This one is by Christopher Day, another renowned Homeopathic vet, this one gives info on nosodes.

The Canine Vaccination IssueChristopher Day MA VetMB Cert IAVH VetFFHom MRCVS(updated November 2002)For more information, visit www.alternativevet.orgA paper written by Christopher Day in his personal capacity as a veterinarysurgeon. Its publication does not imply any corporate agreement, with theviews expressed therein, by any organisation with which he is associated. Itexpresses the author’s own opinions only, and is offered to readers in goodfaith, in order to help them in their decision-making efforts.This paper applies to the UK situation and therefore may not be validinternationally.IntroductionThe subject of vaccination in dogs has been in the forefront of dog-relatednews for several years. As always, the issue sparks heated debate and tendsto produce polarised and strongly held opinions, eloquently expressed byprotagonists on both ‘sides’. It is very difficult to extricate the realscience from the emotive argument, but some balance is needed. The dogs,which are dependent upon us all for their welfare, deserve our concern andour earnest endeavours to steer a responsible path. We cannot duck thisissue on their behalf.The main debate has recently orbited around the question of whether or notannual boosters are necessary or wise, but the wider issue of whether tovaccinate at all still remains. There is also the question of how to test,effectively and meaningfully, a dog’s ‘immune status’ at any given time,possibly with a view to ‘strategic’ boosting.The current prominence of the vaccine issue, especially with regard topossible ill-effects, has led to increasing numbers of dogs not being givenannual boosters and some never being given even the primary course. This iscausing many people legitimate concerns and the voices of fear and anxietyare being clearly heard. It is not difficult to understand the fear, sinceno one wishes to see ill dogs, suffering from preventable and seriousdiseases. For this reason, some clarification is necessary.It is useful, in the interests of clarity, to divide the subject into themain disease areas and to look at those, and the various other components ofthe subject, individually, in order better to comprehend the issues, thesituation and the state of current knowledge. Firstly however, it is ofvalue to make some general observations.GeneralIndividual disease situations vary enormously in their behaviour andimplications. Vaccines vary also and each has different properties andsignificance for its target animals. It is therefore very dangerous to makeany sweeping generalisations across the board of all diseases or of allvaccines. One must try to be selective in examining and discussing thesubject, and to be careful to specify which disease is being considered ineach instance. When assessing the question of vaccination, in any givenclinical situation or hypothetical disease scenario, it is worth taking intoaccount several factors, arriving at a final decision only after weighingthem all together carefully. The factors are:- The prevalence of the disease- The seriousness of the disease- The efficacy of current conventional vaccination- The extent and seriousness of adverse effects of vaccination- The efficiency of any homœopathic ‘buffer’ (a medicine given to shield thebody from some of the ill-effects of vaccination)- The availability of the homœopathic alternative to vaccination(homœoprophylactic nosodes) from a reputable source- The ability to treat the disease if it occursLet us take the hypothetical case of Tetanus, for instance, in man, horses,cattle and sheep, as an example to illustrate the use of this ‘formula’,leaving aside tetanus in dogs until the next paragraph. The disease is aconstant risk, with undetected injuries in animals being an ever-presentfear. The disease is extremely serious and can prove fatal. The currentvaccine is proven, over a great many decades, to be very effective. Obviousside effects or detectable adverse effects are rare. The homœopathic ‘buffer’ appears to be effective. While homœopathic ‘nosodes’ are available, it isnonetheless extremely difficult to test their efficacy, since the disease isunpredictably sporadic, does not occur in outbreaks (except for tetanus fromendogenous toxins in cattle) and failure means possible death of the victim.If vaccination were to be considered, then one would advocate much lessfrequent boosting in animals than is the currently the norm. It is oftendone annually or biennially in horses, for instance, with no scientificmerit for this policy, but every ten years in humans! One would alsorecommend a homœopathic ‘buffer’ to reduce potential adverse effects.In the case of dogs and tetanus, quite why vaccine is not being ‘pushed’,for all the above honourable reasons, is not clear. I have seen at least tencases of tetanus in dogs, in twenty-seven years of practice, and allrecovered with the aid of homœopathic medication. They were distressingcases at the time, nevertheless. While this is not a heavy incidence,tetanus in dogs is not uncommon in certain areas of the country, notablyBerkshire, Oxfordshire and Cambridgeshire. The author does not, however,advocate vaccination against tetanus in dogs, on account of the followingfactors. It is of sporadic incidence, it is susceptible to homœopathictreatment, predisposing wounds are usually noticed immediately in dogs, soallowing ‘specific’ preventive homœopathic medicines to be used and a nosodeis available for general prevention. It is important to note, however, thatto test a nosode’s efficacy against this sporadic disease, by whatevermeans, is likely to prove extremely difficult.Kennel Cough (Infectious Canine Tracheobronchitis)Vaccine components against this disease complex are usual ingredients of themodern compound polyvalent canine vaccines (the relevant fraction is usuallydesignated Pi). There is also an older intranasal (Bordetella) vaccine. Letus apply the same formula to this disease as we did for Tetanus. The diseaseis widespread and common. It is not usually at all serious. The availablevaccines are widely considered to be of marginal value. The adverse effectsof modern kennel cough vaccine alone are not separable from the rest of thevaccine complex, since it is almost never given alone. When the intranasalvaccine was given alone, many people complained that it set up symptoms ofmild kennel cough in their dogs. It was also a very unpleasant physical andpsychological experience for the dog. A study carried out in 1985 showedboth the intranasal vaccine of the period, and the only injectable oneavailable at the time, to be worse than ineffective. They both appeared toreduce the dogs’ resistance to kennel cough and to reduce their response tohomœopathic prevention. This work is about to be repeated, in order to testmodern versions. To test the efficacy of the ‘buffer’ against injectablekennel cough vaccine alone is not currently possible, since that componentis not given alone. It is known, however, that the homœopathic compound‘buffer’ is not able to afford full protection against the ill-effects ofthe modern complex polyvalent vaccines as a whole. The homœopathicalternative to kennel cough vaccine (nosode) is readily available. One‘version’ of it was well-tested in the above-mentioned study and was foundto be very effective. This result appears to be borne out ‘in the field’.The disease is eminently treatable by homœopathy, symptoms of coughing beingcleared within three days, as a norm. (By way of contrast, in the case oftreatment with antibiotics, as many readers will know, kennel cough usuallybrings three weeks of sleepless nights!) In summary therefore, if theformula were to be applied, one would not advocate conventional vaccinationagainst kennel cough.LeptospirosisLeptospirosis is not a single disease. There are two main bacterial typeswhich can affect dogs and both are related to very dangerous diseases intheir own right. Leptospira canicola affects the kidneys of dogs, causingsevere and often fatal damage. Leptospira icterohæmorrhagiæ affects theliver, producing dangerous jaundice (Weil’s Disease). There are many otherstrains and species of Leptospira, but these are the main two ofsignificance in dogs. It is known that circulating antibody levels, producedby conventional vaccine, do not last as long as a year in some cases, but itis not known how long actual immunity lasts after vaccination. The vaccineis the ‘killed’ component of modern polyvalent vaccines and, because it isin liquid form, it is usually used as the diluent for the other ‘living’(freeze-dried) components. If we again apply the formula, we can objectivelyassess the wisdom or advisability of vaccination against these two diseases.The diseases are not prevalent but are widespread. They are transmissiblefrom rivers and ditches, or from infected dog urine. They are both seriousdiseases. The current vaccines seem reasonably effective, but it is notknown for how long they last. It may be for less than the year that isallowed between boosters. Adverse effects are not well-documented and wewould really only know about these if the components were to be givenseparately. On some occasions, this component has been given alone, in orderto reduce the annual vaccine burden, with recorded adverse effects. The samecomments apply for the ‘buffer’, as were discussed above for the KennelCough situation. The homœopathic alternative (nosode) is widely available.The diseases, while serious, life-threatening and unpleasant, have provedtreatable by homœopathy in most cases encountered. The result of thisexercise is to leave one feeling a little ambivalent toward vaccination forLeptospirosis. Some people are now asking vets for this vaccine componentalone, and are using circulating antibody levels as a guide to the need forit. This somewhat separate topic of antibody testing is discussed in moredetail later but it is of very questionable value, especially in the case ofthis disease. The author has never had cause to regret not using thevaccine, all patients having been given the homœoprophylactic nosode, withno breakdowns, over many years.Distemper (Hardpad)/Hepatitis /ParvovirusThese three diseases together give us the acronym DHP and are ‘living’ viruscomponents of the usual vaccination course. These are the three deadly virusdiseases of dogs and are rightly to be feared. Viral hepatitis is very rarenow, thanks in part to the vaccination programmes undertaken since the ‘60’s. Overt signs of adverse vaccine reactions are now rare, but in the earlydays the ‘blue eye’ syndrome was not uncommon following vaccination. Thiswas apparently due to impurities in the hepatitis vaccine. Distemper is alsorarely seen in vaccinated dogs. Parvovirus was a newcomer on the scene, inthe ‘70’s, and it is not clear whence it came. It had disturbingsimilarities to Feline Enteritis virus and is also, happily, quite rare butdefinitely not unknown in vaccinated dogs.The clear benefit that vaccination has brought in the case of these diseasesis to be welcomed, but the modern concerns about adverse vaccination effectscentre on these three. There is particular concern over the habit of annualboosting. A great many cases of chronic diseases appear to start withinthree months of a vaccination event, whether that is the primary dose or asubsequent booster. This disturbing pattern needs investigating, but thereis a fuller discussion later in the paper. Applying the ‘formula’, however,puts a rigid vaccination policy in doubt. The diseases are not prevalent butsoon could be, if all controls were to be relaxed. The diseases are serious,to the point of potential lethality. The current vaccines appear broadly tobe effective. The extent of adverse reactions is the contentious issue andthe data which are emerging do indeed require a satisfactory alternativeexplanation, if they are to be deemed not to be the result of vaccination.The homœopathic ‘buffer’ appears only to be partially effective. A recentmemorable and distressing case (Christmas ‘9, of a puppy dying slowly withmeningitis-type symptoms within weeks of primary vaccination, despite beinggiven a ‘buffer’, serves as a salutary reminder. The homœopathicalternatives to vaccination are widely available and the author has had nobreakdowns in his patients, recorded over many years. The diseases are onlyrelatively amenable to homœopathic treatment, should they occur, so oneshould not be absolutely confident of therapeutic success. Weighing andconsidering all these reasons together, a policy of routine nosodeadministration, rather than vaccination, would seem to be advisable (adiscussion of the important subject of the efficacy of the method followslater).RabiesThis disease, although not present in the UK at the time of writing, iscurrently very much in the news on the quarantine question. Since it is a‘notifiable’ disease and subject to legal regulations, it will not be alarge feature of this article. Suffice it to say, however, that the‘exchange’ for dropping quarantine, when bringing a cat or dog in fromEurope, is a legal requirement for rabies vaccination, for microchipidentification and for a flea/tick/lice/mites treatment just prior to entryto the UK.In the US, where rabies vaccination is a legally required routine, there aremany reports of serious adverse reactions. Many US veterinarians arebecoming very concerned on the issue.The clause about ectoparasite treatment, while not strictly relevant to thispaper, may also be a cause for anxiety, depending upon the product used.Organophosphate products are now known to be very unsafe, for animals andfor human ‘contacts’. The more modern compounds have been associated by somepeople with neurotoxic effects.The polyvalency issueIt is widely believed, with some justification, that it is unwise or evendangerous simultaneously to combine vaccine challenges for so many diseases.It stands to reason that the body’s ability properly to react may becompromised by such a habit of convenience. The vaccines available, when theauthor qualified in 1972, only contained components for four diseases. Itwas not long before Parvo was added, to make a fifth. One brand thenemerged, which contained a ‘kennel cough’ fraction and, with other‘improvements’, comprised seven components. It is now fashionable to marketvaccines mostly with six components, with one or two brands being ‘seven inone’. The vaccine challenge presented by at least four of these is verystrong. How is the body to be expected both to withstand this multiple‘attack’ and adequately to respond to each?The annual booster issueThe habit of annual boosting has come under scrutiny recently and,certainly, it is an unscientific practice. There is no science to supportthe policy but it appears to be based on the fact that vaccines are onlytested for one year. Annual doses are therefore given ‘in case’. One canpicture an analogy of a lion in a cage being bated with a stick that ispoked through the bars. It will react appropriately and vigorously at first.If, however, it is repeatedly provoked in this way, there will come a timewhen it no longer responds. It will be exhausted. The immune system canrespond similarly to repeated stimuli.There is also the issue of antibody testing, which is sometimes erroneouslythought to be equivalent to immunity testing. The whole subject of immunityis little understood as yet but it is known that immunity does not restsolely with circulating antibodies. What is required for a good immunedefence is a sensitised and healthy immune system. This may mean that, inmany cases, one dose of an effective vaccine could last for life. The authorbelieves and contends that antibody testing is neither a valid nor a safemethod of assessing the need for revaccination.What the author feels to be totally insupportable is the habit of giving a‘double’ course of injections to a dog whose annual boosters have lapsed fora period. There is no science behind that practice and it appears to bringwith it some very serious dangers.The concept of a healthy immune system also brings in the issue of a healthydiet, to maximise immune health. In the author’s opinion, this means freshvaried food, from as pure a source as possible, preferably organic. Immunehealth is not best served by the canned, bagged and processed foods, whichseems to prevail in the modern dog’s life, to its serious detriment.The ‘age at primary vaccination’ issueThe age of the puppy at first vaccination has to play a part in its abilityto withstand vaccination. Puppies are not born with ‘maternally-derived’immunity, as in the case of human babies, but must obtain a supply ofantibodies from their dam’s first milk (colostrum). This has at least twofunctions. One is to aid the puppy’s immature and unready immune system,temporarily, in warding off those infective challenges of which the dam hasexperience. The other, and probably just as important function, is to savethe puppy’s immune system from over-reacting to challenges, during theperiod that it requires to find a proper balance.Into this immature, delicate, developing process, including physicaldevelopment of brain, skeleton, nervous system, glandular system, teeth andother organs, we introduce the intentionally violent challenge ofvaccination. Not only is the route of ‘infection’ an unnatural one, takingthe immature immune system ‘from behind’, whence it has not evolved toexpect a challenge but also, the challenge is designed to be violent enoughto sweep aside the maternal ‘buffer’. This exposes the immature immunesystem to an unmitigated attack. If, on the other hand, an unfortunate puppywere to happen to have an inadequate or abnormally low level of passivematernal immunity at the time of primary vaccination, then this could bedisastrous. The surplus vaccinal challenge, which is designed to brush asidea normal level of maternal immunity, will also be unleashed on theunfortunate puppy. This would effectively amount to a ‘double’ dose and mayexplain some of the variability in susceptibility, which we observe inpractice.The possible noxious effects of the vaccine challenge on this developing andvulnerable body are legion. One can cite some examples. There may be damageto immune balance, impairment of immune capability, stimulation ofautoimmune processes, disorders of behaviour, disruption of delicatedevelopmental and growth processes (eg skeletal problems, non-descent oftesticles) or triggering of hereditary or congenital tendencies. Therecertainly appear to be breed susceptibility traits, German Shepherds, GoldenRetrievers, Cavaliers and Irish Setters seeming to be among those moresusceptible to adverse vaccine reactions. There may even be frankinflammation or infection, with live virus, of the target organs of eachvaccine component. We could have an explanation here, not only for manypuppyhood diseases and problems which start between three and six months ofage, but also for the prevalence of many of those developmentalabnormalities, which have not hitherto been identified as having a directand simple hereditary cause.It seems logical, if vaccination is really considered to be a necessarytool, that puppies should be vaccinated as late in their delicatedevelopmental phase as possible. This allows uninterrupted normaldevelopment of brain, synapses (connections within the central nervoussystem), skeleton (bones and joints), immune system, heart and all organsystems, prior to the anticipated shock of vaccination. This does not meanthat an adult or adolescent dog is ‘immune’ to the potential ill-effects ofvaccination, far from it, but it does stand to reason that it should bebetter able to cope, and that those vital development processes are alreadysafely completed or nearing completion.The miracles of normal conception, fœtal development, birth, post-natalgrowth and post-natal development cannot be taken for granted. It seems thatwe do tend to do just that, however and we even expect that system towithstand severe intentional challenges to its integrity. It is notbomb-proof and we are often or rather puppies are often, it seems, payingthe price for that dangerous assumption.The dose issueA custom, which confuses many, is that of giving a Chihuahua puppy (forexample) the exact same dose of vaccine as that given to a Great Dane adult.It is said, by those who support this practice, that the stimulus dose ofantigen required is the same in each individual, whatever the size. That mayor may not be the case and probably remains to be proven, but what isignored in that argument is the dose of the other materials in the vaccine,which are often not discussed. It also ignores the question of individualsensitivity, which must influence very directly the response of eachindividual, of whatever breed or size, to the vaccine challenge. This latterextremely important parameter is unfortunately not measurable prior togiving the vaccine. We can only determine retrospectively, whether anindividual was ‘too’ sensitive.The ‘health at vaccination’ issue.The ‘data sheets’ of all vaccine products rightly state, as a firstprecaution, that only healthy animals should be vaccinated. It is smallwonder that there are many problems with vaccination, when so many animals,which are clearly suffering from immune-related disease, for example: skinproblems, colitis, pancreatitis, fits, asthmatic-type conditions,auto-immune complexes and many others, are still relentlessly vaccinatedeach year. The question of ‘health at vaccination’ is left to the individualveterinarian involved at the time and there are no guidelines offered. If anunhealthy animal is vaccinated, this represents an ‘off label’ use of thevaccine which is, strictly speaking, contravening the regulations whichgovern the use of medicines.Possible mechanisms of damageIt is not widely considered, by the conventional veterinary community, thatvaccines can be damaging. The strong desire to prevent disease not onlydrives veterinary surgeons to maintain vaccination policies, but also fuelsthe search for new vaccines for any disease considered possibly to have aninfective component. This process has become so accepted that it is littlequestioned. The fact that those who develop vaccines and those who sell themare making money from the practice is a side issue. There is generally avery strong will to prevent avoidable suffering.When overt vaccine reactions occur, however serious may be themanifestation, they are considered to be few and to be of less importancethan the issue of protecting the majority of the population. The result isthat even overt and obvious vaccine reactions are rarely reported to theVeterinary Medicines Directorate, on form MLA 252A. This is only a voluntaryscheme and is vastly under-used. The computers allocated to the task ofsifting data, in order to collate and to assess any number of reports whichmay be made, are grossly under-utilised. The scheme is supposed to attractreports of any ‘suspect’ adverse reaction to drugs or other medicines,including failure to perform as expected, and puts no burden ofinvestigation or verification upon the reporter. It is even named the‘Suspect Adverse Reaction Surveillance Scheme’ to reinforce that point.Verification is the purpose and task of all that computer capacity.Computers are very good at number crunching and establishing anddemonstrating patterns and trends. They are no good at telepathy.What is never reported, mostly because it is neither noticed nor recognised,is the much more prevalent phenomenon of ‘occult’ vaccine reactions,so-called because their association with a vaccination event is notimmediately apparent. These reactions become manifest in the monthsfollowing a vaccination event, possibly over an indefinite period, dependingupon the nature and dynamics of the immune disturbance and its symptoms. Themajority, however, occur in the first three months after vaccination. Theway in which these reactions can be detected and identified is by a verycareful process of enquiry, in order to establish the very first noticeablesigns of the chain of events leading to chronic disease. In the author’sveterinary referral practice, for instance, eighty per cent of chronic skindisorders are reported, in those cases in which a start date can beretrospectively identified with any confidence after very exhaustivequestioning, to have started within three months of a vaccination event.That is highly suspicious of evidence of a vaccine effect. This statisticrequires an equally logical and cohesive alternative explanation, if it isnot to be classed as a vaccine reaction.It is easy, hypothetically, to explain this ‘delay’ phenomenon. If thevaccine (whatever component or ingredient) were to disturb the delicate yetvital immune balance, which is so essential to daily health, in such a waythat it is not able to self-correct, then the body will only graduallydevelop symptoms as the effects of the disturbance take effect. The rapidityof onset and the seriousness of the symptoms would reflect the depth andextent of the disturbance of that balance.One way in which this disturbance may be observed is in the ‘specialisation’of immune resources. The undisturbed immune system retains a capacity forresponse to a vast diversity of potential challenges. Vaccination againstspecific infectious diseases can tend to specialise the immune capability,thus reducing its potential array of responses to other ‘attacks’, mountedfrom hitherto unexpected directions. The military analogy would be an armyprepared, equipped, trained and deployed for an attack from a certain borderof the empire, only to be taken off guard by an incursion from the oppositedirection, in climatic and topographical conditions for which it is neitherequipped nor trained. The necessary translocation, re-equipping, retraining,and redeployment would be much more difficult and time-consuming than if thearmy had been centrally placed and partially readied for a variety ofpossible invasions.Another possible mechanism for damage to the body by vaccination is theintroduction of ‘stray’ undetected infective agents. This is a known andalready experienced effect of vaccination, with some disastrous results inhumans on record. There is also the fact that vaccines can carry residues oftissue from other species, or from other individuals of the same species.These residues can spark a severe reaction or even trigger autoimmunereactions, to similar tissues in the subject’s body. Vaccines can also carrya range of other foreign materials, to which the target individual can react‘adversely’. These may include such substances as preservatives,antibiotics, adjuvants, heavy metals, solvents, anti-virals and coatingsfrom syringes or needles.The homœopathic alternative to vaccinationThe homœopathic method has been in use for a great many years, and there arelegions of users out there who would assert its value. The author’s ownanimals, dogs, cats and (rescue) horses have been stalwart examples. Hiscurrent dog is eleven years old, has never been vaccinated at all, has froma very tender age been to all the places one would not take a dog if tryingto avoid infection and yet has never suffered a day’s illness. None of hiscats have ever been vaccinated for the last twenty years. The older oneshave died in natural old age when the time has come, those alive have livedvery healthy lives without any veterinary interference and yet have metkiller viruses, from confirmed sufferers of most of the nasty virus diseasesof cats, on an almost weekly basis. His horses have been special examples,in that they have all totally resisted a virus which swept through a yard atwhich they were stabled, dragging down every other horse, all of whom hadbeen vaccinated.The problem is that there is currently a lack of scientific proof ofefficacy of the method. There is also no way of testing the quality of thevarious manufacturers’ products. There is, however, a huge weight ofanecdotal evidence to support the use of nosodes in all the domesticspecies, some clinical trial work in dogs, and strong analogous evidencefrom clinical trial work in similar applications in farm species. Thisinformation alone is very compelling. Its advantages (not in order ofimportance) are that it is cheap, it can be given at home by the owner, itdoes not involve injection and its use is free from harmful side effects.The lack of scientific proof of the method stems from the fact that thereare no multi-millions put aside to research it, unlike conventionalvaccines, because there would be so little profit for anyone, from marketingit, at the end of the day.Furthermore, protocols proposed to research the homœopathic method hithertohave involved the use of ‘laboratory’ animal experiments, with artificialviral challenges to test efficacy. This would cause the author a seriouspersonal problem, not least since unprotected ‘control’ animals would alsobe used, for whom a viral challenge would undoubtedly cause disease. As aveterinary surgeon he simply feels unable to do that and the oath, takenwhen he qualified as a vet, explicitly and rightly forbids it. That is whyhe has not participated in some of the trials offered to date.What is needed is a series of clinical trials, run under ‘field’ conditions,but these are difficult to design and to interpret, expensive andtime-consuming to perform and would have to run over long periods. Whencomparing this to the far simpler and cheaper laboratory methods, it is easyto see why the commercial ‘scientific’ world uses animals in laboratories inthe current fashion. One example of a study of the homœopathic preventiveagainst kennel cough is shown below.A clinical study conducted in a naturally-occurring outbreak of Kennel Coughin a boarding kennel, in May 19851. At outsetogs in kennel: 40Dogs affected: 37(of these 40 dogs, 18 had been vaccinated against Kennel Cough prior toentry, all 18 of those contracted frank Kennel Cough. The three unaffectedindividuals had received no Kennel Cough vaccine)2. After giving ‘nosode’ to each new incumbent, at time of entryogs in kennel: 214Dogs affected : 4(of these 214 dogs, 64 had been vaccinated against Kennel Cough prior toadmission, 3 of those contracted frank Kennel Cough. This means that only 1of the 150 non-vaccinates went down with the disease)Full trial data posted on www.alternativevet.org .The fear of a disastrous outbreak of viral diseases in dogs, were manypeople to refuse vaccination for their charges, is probably overstated.Responsible people are not advocating a policy of ‘no prevention’. Those whoare not having vaccines for their dogs are not neglecting their duty ofcare, they are taking up homœopathic protection efforts after serious studyof all the available information. Most are people whose dogs have sufferedvaccine reactions in the past. Many are those with animals who are not‘healthy’, so can not correctly receive conventional vaccination anyway. Inthe extremely unlikely event that any of these dogs should become ill withone of the preventable diseases, their carers will seek homœopathictreatment immediately, which is usually very effective, both to lessen theseriousness of the illness and to speed the recovery.AvailabilityThe nosodes are easily available, but it is best to seek advice from aveterinary surgeon about obtaining them. Too many people are happy to sellthem with no proper explanation or instructions. The author has heard of oneor two ‘breakdowns’ with some suppliers’ material. This may be due to lackof quality or to inadequate instructions or to an incorrect régime or tocombinations of these possibilities. This is a good reason to seek properlyinformed veterinary advice. The Veterinary Surgeons Act (196 and the lackof indemnity insurance for ‘lay’ prescribers are other potent incentives todo this. The recorded experience of the author, with nosodes, is based onthe use of his own product. For this reason, he is unable to say whetherother products would perform better or worse or what is an ideal régime forany other product.While a large proportion of veterinary surgeons, who use alternativemedicines, are aware of the dangers of vaccination, only a very few are nowoffering or providing homœopathic alternatives with any confidence orconsistency. Each individual veterinary surgeon holds his or her ownopinions and anxieties. It is difficult to throw off the fears, instilled byyears of training, that the serious diseases will not be prevented otherthan by vaccination. It is also a hard economic decision to give up theincome from vaccination. Nonetheless, it is possible that most of theseveterinary surgeons could provide nosodes on request. Prospective usersshould make due enquiry in advance. In the author’s opinion, it is importantto obtain these products, and to use them, under properly informedveterinary supervision.SummaryWhen we look at the beliefs surrounding currently available conventionalvaccines, we see a very confused picture. A large sector of the dog-caringcommunity asserts that the use of vaccines brings serious dangers,experienced by many dogs in a very real way. The ‘scientific’ community, onthe other hand, asserts that vaccination risks remarkably little by way ofside effects, quoting the paucity of reports lodged with the voluntary (andmuch under-used) Suspect Adverse Reaction Surveillance Scheme, run by theVeterinary Medicines Directorate, as proof of this. A much greatersensitivity is required, to the issues involved and to the phenomena ofadverse effects, if we are fully to understand the problem and be able torecognise the sequelæ.The author’s records show a significant number of dogs showing first signsof chronic disease within the three months following a vaccination event.Such diseases as skin problems, anæmia, chronic fatigue/malaise, chronicbowel and digestive disorders, pancreatic insufficiency, epilepsy,autoimmune disease, even CDRM (in several German Shepherds a few weeks afterdouble boosting on account of lapsed annual injections) are among these.There are other, perhaps more surprising, diseases with which there arestrong circumstantial links to vaccination events. Among theses arecardiomyopathy (eg Danes and Dobermanns) and heart valve disease (egCavaliers). There are clearly also breed tendencies involved in thisfinding, perhaps with vaccination as one of the potential triggers tomanifestation. There are also cases of diseases, once thought to have beencured with homœopathy, which have relapsed soon after booster vaccination.These phenomena are even more noticeable when a dog has been started on anew course of the two initial injections, following a temporary lapse inannual boosting. In the author’s opinion, this latter ‘habit’ is the mostdangerous and least scientific of our vaccination customs. There is noscientific support for annual boosting anyway, let alone for restarting acourse in this arbitrary way. There appears to be a heavy reliance placed onmonitoring of circulating antibodies as a measure of immunity. This is notgood science, since it is known that real immunity runs much deeper thanthat, and at local tissue level too, and that circulating antibodies are avery specialised and narrow facet of the animal’s total immune capability.While the circumstantial evidence for adverse reaction ætiology is strong,in the case of many of these mentioned diseases, the reader must be awarethat a link is not proven in many of the examples mentioned above. Opinionsshould be formed bearing that in mind.The way forwardWhat should the caring dog person or worried veterinary surgeon now do, withhis or her advisors so torn on the issue? Firstly, it is not wicked tofollow instincts. Secondly, it is not irresponsible to act upon widereading, upon personal experience, upon the experience of one’s colleaguesand peers and upon intuitive motivation. Thirdly, it is sensible tointerpret any received advice in the light of any potential vested interestof the advisors in question. Fourthly, it is irresponsible to do absolutelynothing for reasons of laziness, apathy, short-term economy, ignorance orneglect.It is necessary, in order to satisfy one’s self that one is actingresponsibly, to read widely, to examine the evidence and to seek advice on abroad front. Possibly most importantly, it is necessary to monitor theresults of one’s decision constantly, carefully and objectively, to reviewany policy in the light of that information and to act upon the basis ofthat review.Copyright © Christopher Day MRCVSAlternative Veterinary Medicine CentreChinham HouseStanford in the ValeOxon SN7 8NQTel: 01367 710324Fax: 01367 718243www.alternativevet.org

Christine.

Some experts discussing it here

December 1988 issue of DVM magazine featured this Vaccine Roundtable discussion.Safety, efficacy heart of vaccine use; experts discuss pros, consModified live virus veterinary vaccines developed during the past two decades have been very effective in reducing the incidence of viral diseases in many species of domestic animals. Now, an increasing number of new, inactivated virus vaccines are being produced and more will be available in the future. Discussing the advantages and disadvantages of both types of vaccines in our exclusive roundtable, co-sponsored by Diamond Scientific, and hold at the Salk Institute in San Diego, are; Dr. Ted Rude, founder of Veterinary Consulting Services in Hudson, Wis., a consulting firm for the veterinary biologic and pharmaceutical industry in pathology, toxicology, forensic veterinary medicine, biological development and vaccination programs in domestic animals and poultry. He is a graduate of the University of Pennsylvania and a diplomate, American College of Veterinary Pathologists; Dr. Ian Tizard is professor and head of the Department of Veterinary Microbiology and Parasitology at Texas A&M University. He received his DVM degree from the University of Edinburgh and his Ph.D from Cambridge University; Dr. Gunter Siegl is head of the Department of Virology at the University of Bern, Switzerland, where he oversees experimental virology, diagnostic virology as well as AIDS research. He received his Ph.D degree from the University of Munich; Dr. Ran Schultz is professor and chairman of the Department of Pathobiological Sciences at the University of Wisconsin Madison School of Veterinary Medicine and holds joint appointments in the Medical School and the Department of Veterinary Science, College of Agricultural and Life Sciences. His undergraduate and graduate training in bacteriology biochemistry, immunology and pathology were done at Pennsylvania State University; Dr. Jonas Salk is founding director and distinguished professor in international health sciences at the Salk Institute for Biological Studies in San Diego Calif. He received his MD degree from New York University College of Medicine in 1939. Along with his lifelong biological research especially polio he has held professor and fellow positions at the University of California-San Diego, University of Pittsburgh School of Medicine, University of Michigan School of Public Health, Department of Epidemiology. His brother is a veterinarian; Dr. Larry Swango is associate professor of Virology in the Department of Pathobiology, College of Veterinary Medicine, Auburn University. His primary area of research has been with canine virus diseases and vaccines. He received his DVM degree from Oklahoma State University. Rude: What is the rationale for the use of modified I live virus vaccines in domestic animals and why have they been so successful during the past two decades in reducing the incidence of various diseases in domestic animals?Swango: Certainly, modified live virus vaccines have made a very valuable contribution in the control of infectious diseases in domestic animals. One of their strong points has been the simulation of a natural infection and immunity in response to replication of the virus within a host. We can go back perhaps more than two decades with the introduction of rabies vaccines for a little historical background. At that time, rabies was a disease of great significance in the United States and other developing countries. We needed something to control it and the live virus vaccines that were initially used were very effective in controlling the disease. As we began to control the disease, we then became aware of vaccine-induced disease in which we could then switch our emphasis to increasing safety to further attenuation. One of the strong points of the modified live virus vaccine is the fact that in the animal, it stimulates immunity based on replication of a virus which stimulates an infection with a non-virulent strain of virus.Siegl: I would just add that one of the advantages of modified live virus vaccines is the fact you usually need to vaccinate only once with the virus. In general, you also need a relatively small dose of vaccine. The modified live virus contained in it replicates in the animal and induces an immune response comparable to the one obtained after exposure to the wild-type virus.Salk: Well, there are advantages and disadvantages as already mentioned, and I suppose it's appropriate to consider modified live virus vaccines in the evolutionary development of the ultimate which would be not merely to simulate nature, but to improve upon nature. So perhaps we should look upon this discussion, and this point, about advantages and disadvantages relative to where we stand in our science and technology.Schultz: I believe the history on modified live viral vaccines, especially in veterinary medicine, stands as an example of how effective and how safe certain modified live products really are. Dr. Swango mentioned the example of rabies. I think the examples of feline and canine distemper and canine adenovirus are equally good examples of effective modified live viral vaccines in small animal medicine. We also have examples in large animal medicine In which we can show both safety and efficacy for these products because they do produce protective immune responses, and that is what we're attempting to get from our modified live products.Protective immunity is a very different concept from simply inducing a serologic response. As the discussion continues I think we can get into the details of why and how a modified live product can provide a protective response, humoral and cellular, local and systemic, whereas we may not be able to get a protective response from certain inactivated or sub-unit or synthetic products.Tizard: But having said that, it appears, as Dr. Sulk said, that the production of vaccines is an evolutionary process and in the past, it has proven easier to make modified live vaccines than inactivated ones. They overcome a lot of shortcomings in terms of adjuvants, in terms of ways of preparing antigen, and most economically, in terms of antigen dosage. You can produce them very cheaply. One could argue, however, that they are not as devoid of side effects as we would like to think. When, we started to control diseases like canine distemper, those side effects were minor concerns. While we certainly have to give credit to modified live veterinary vaccines for having had a tremendous impact in controlling disease in this country, they do represent a fairly basic technology that can be improved upon. Many of the disadvantages of inactivated products have now been overcome.Rude: Dr. Swango, you mentioned something about vaccine-induced disease and there are some reports about disease in vaccinated animals. Since you are primarily in canine vaccine research, what modified live virus vaccines is the canine area are most likely to do this and how serious is the problem?Swango: Probably some of our least attenuated canine distemper vaccines, when used in a very young animal that does not have a fully developed immune system, are where some of our greatest risks lie. We have some very good distemper vaccines. Modified live distemper vaccines, when used in the animal at an age for which they were developed and intended to be used, are relatively safe. But when used in a younger animal in which the immune system has not developed to the point of being able to respond and contain the modified live virus antigen, then we do get vaccine induced disease.Rude: In your research experience, Dr. Swango, what particular vaccines can you cite as causing vaccine-induced diseases?Swango: Canine distemper in, again, very young puppies. Certain strains of modified live canine distemper virus can cause disease in very young puppies If we broaden our perspective of disease to indicate and to include any pathological condition, not necessarily the typical disease, then we would have to refer back to a very low rate of pathologic change associated with canine adenovirus Type I as a modified live virus vaccine.Tizard: And you talking about " blue eyes?"Swango: "Blue eye" and perhaps renal lesions in some instances. Those would be adverse effects, a disadvantage of the vaccine, but not causing the typical disease. There has been a great deal of interest in the last eight to 10 years about modified live canine parvo vaccines causing disease in dogs. I have yet to see a modified live canine Parvo virus cause disease in a dog.Rude: When you talk about younger dogs, Dr. Swango, can you be more specific on week of age in these dogs?Swango: Any animal under 4 weeks of age, but extending even on to 6 to 8-weeks of age in some instances. Now this may be a function of genetics of that breed or that bloodline, but we have some indication that even in 8 to 8-week-old puppies the distemper vaccine may occasionally induce disease. There may be some con-current factors, other infections or something that contributes to that, but especially in puppies under 4 weeks of age.Rude: There have been reports in the literature about chronic canine distemper and old dog encephalitis. Chronic canine distemper is usually seen in young dog 2 to 3 years old, whereas old dog encephalitis may be seen in dogs 5 years of age or older. Many of these dogs have been vaccinated as puppies with modified live virus canine distemper vaccines. Do you believe there may be a connection between old dog encephalitis or chronic distemper and the use of these vaccines?Swango: The difficulty of reproducing those chronic infections experimentally has complicated our interpretation and assessment of the role the distemper vaccine may be playing there I do know that this distemper virus can be isolated from lymphoid tissue of vaccinated puppies, in some instances a much as six weeks after vaccination. It's difficult sometimes to prove that it's a distemper vaccine strain of virus rather than a virulent field strain. In some recent isolations that we have made, in which it was very easy to isolate the virus in cell cultures that normally do not support replication of field strains, we're inclined to think that certainly we can get some persistence of the view in the vaccinated animal. Now whether this contributes to the chronic distemper and the question you're raising, I'm not sure.Tizard: In making a modified live vaccine you make it for an animal that you assume is immunologically normal. Essentially you're doing a balancing act; taking an agent and attenuating it so that in the immunologically competent host, (the normal animal), it will not cause disease. The trouble is, you cannot assume that every animal you vaccinate is functioning immunologically normal. There will be a proportion of any population that is not immunologically 100 percent. This can immediately tilt an animal towards disease susceptibility. In addition, a vaccine may not cause freak disease itself. It may cause mild immunosuppression.Salk: Discussion, even at this early stage, brings me back to the days when I heard, in 1936, that it was not possible to immunize against a virus disease with a killed virus vaccine We've come a long way and now we're on the threshold of being able to eliminate vaccine risks. There is a tendency to want to eliminate all vaccine associated disease both in the human realm and in the veterinary, realm. I think we're appropriately reevaluating and reexamining the question as to whether any risk is necessary. Can we not do so with killed virus vaccine* and even improve upon nature by combining many viruses into a single vaccine using the adjuvants that make this possible? There is a problem of vaccine-associated disease that cannot be avoided.Rude: Dr. Swango, world you like to comment?Swango: Dr. Tizard made a comment that I think may require some response at this point. It is true, we can't be assured that 100 percent of the animals will respond to vaccinations. I'd like to extend his comment to an area that I feel, in veterinary medicine, we have perhaps been remiss in leading our profession as well as the public to believe that if we use Vaccines, we can guarantees 100 percent success in immunization. Then when then is a problem that develops in a vaccinated animal, people an greatly concerns. So I think some of the going Dr. Tizard mentioned are certainly paramount to this, but I feel that we somehow need to redirect an emphasis that just because we vaccinate, we cannot assure immunity. There is a difference between vaccination and immunization.Rude: Does shedding of modified live virus vaccine viruses from vaccinated animals have the potential to cause disease in non-vaccinated contact animals of the same species and/or different species?Salk: Well, it's self-evident that this is what happens with polio. I have not seen evidence that it is of significant advantage. There's a disadvantage in the U.S. because of vaccine associated disease. In the developing countries live virus vaccines often fail because they don't always protect those who are directly vaccinated due to inhibitors in the intestinal tract. In the U.S., vaccine virus is the principal cause of continuing polio.Schultz: Dr. Salk, is this the vaccine virus itself that, when spread, is causing problems? If that's the case, then we have the spread of a vaccine virus that really is not attenuated. In veterinary medicine, we have some examples of truly attenuated vaccine viruses that spread, but the spread of the vaccine viruses leads to herd immunity which Is a very positive effect within the animal population. We, as well as others, have demonstrated that when spread of the vaccine occurs, there is no reversion to virulence. In fact, some of these viruses remain truly attenuated throughout the animals lifetime because they are viruses that become latent and can be reactivated and can be shown to be truly attenuated five to 10 years after an animal was vaccinated.Salk: What you just described is not my understanding of herd immunity. That's direct Immunization and that ought to be clarified.Schultz: In this case, it is herd immunity. It's within a herd or cattle. So in the context of herd immunity in veterinary medicine, it's real. With regard to 'herd immunity' in human medicine, it may not apply.Siegl: I just want to go back to your final question and to what Dr. Salk said. It has been shown that shedding of virus, especially in the polio virus field, can mean selection of new variant viruses which spread and cause disease. I would say the basic principle, as soon as a live virus is being applied to an individual of a certain species, in that out of the mass of various mutant, as I tried to point out before, you are going to have an opportunity to select for one viral mutant which is able to replicate even in the presence of some sort of immunity. That new selected view can spread within the same species or in a different species.Tizard: I can think of one veterinary example and that's laryngotracheitis in poultry. Vaccines used in the Northeast appear to be pretty good vaccines and are essentially avlrulent. If vaccinated carrier birds are moved, say to the Southwest, these vaccinated birds are a source of infection for the naive flocks sail cause clinical Iaryngotracheitis.Swango: Your original question had to do with, as I recall, modified live viruses shedding from vaccinated animals and affecting not only animals within the species for which it was intended, but other species. I think one example perhaps relates to canine distemper virus, again, and I'll just touch an this briefly. I think Dr. Max Appel at Cornell, has shown, a number of years ago that within a population of virus particles of a modified live distemper vaccine there was a certain small percentage of that population that was still virulent. So in an animal in which there could be selection for enhancement of replication of that small population, then I think we could have reversion of virulence. Maybe in an immunosuppressed or immunodeficient young dog we might have expression of that type of reversion of virulence with transmission to other animals and perhaps not causing a typical, classical, acute distemper, but maybe the chronic infection within the species of what I refer to as strains of low virulence. We have evidence for this type of phenomena when distemper vaccine was used in a different species. A single passage of a modified live virus canine distemper vaccine through a gray fox, in which it was virulent resulted is reversion of virulence for the dog. The virus isolated back from The virus isolated back from the gray fox was no longer attenuated for the dog. So that touches, at least, on the involvement of other species and this problem of shedding and reversion of virulence.Rude: What are the chances of mutant viruses developing in animals vaccinated with modified live virus vaccines; in contact animals of the same species or other species?Siegl: I would say the chances for mutations are quite well understood at present. You have a chance of mutation at about 10-3 to 10-4 for RNA viruses. Rates an about 100 to 1,000 times lower for DNA viruses, but considering the fact that effective replication of a virus produces hundreds of thousands or millions of viruses in the cells of an organism there is always a great number of mutants around. Of course, most of these mutant are not able to survive in that surrounding because they are defective mutations. Nevertheless, we have to consider the fact that this is a Huge pool of genetic material from which new variants can be selected, and as has been pointed out before, it is clear. Especially in the polio virus field, that one passage through the human gut can result in selection of quite a number of new variants. Another situation favoring the appearance of mutations not directly related to vaccination, is persistent infection. We have been talking about persistent infection in context with canine distemper virus. It might be the result of vaccination that as soon as persistent infection is established, the incidence of mutations increases considerably. In addition, we have the possibility of recombination between wild-type virus and attenuated viruses. This might at least to my understanding, produce one of the main problems once we get to the point that we can engineer so-called safe attenuated vaccine. We will hardly be able to exclude the possibility that viruses from such products will recombine with wild-type virus under field conditions. My concern at the moment is the theoretical considerations Nevertheless, there are practical examples available to stress the reality of this problem.Salk: The object of this exercise, it seems to me, is how can we produce biological products with the maximum amount of safety and efficacy? As a theoretician, one can imagine how that can be done. In the meantime, one has to be altogether pragmatic when the disease is of far greater risk than the methods that an employed in their control.Rude: We have talked about mutations of viruses in animals. What are the chances of mutant viruses developing in cell cultures associated with the production of modified live virus vaccine? The second part of this question is what are the chances of harmful, contaminating viruses or adventitions viruses being present in modified live virus vaccines?Schultz: I think that we have plenty of examples where we can demonstrate that, in cell culture, we have failed to attenuate. I think in part, we're getting back to an earlier, more primitive age. Some veterinary vaccine were not made from cloned viruses. Instead, an unknown population of virulent viruses were passed in cell culture and we developed something that was called a modified live attenuated vaccine, but sometime it was a modified live virulent vaccine. I think that if we would come up into the 1980s with the current technology, we would relook at some of the things we've done in the '50's, '60's and '70's. So yes, there is that opportunity with modified live product, to have mutations or variations that can act very differently among species. That's the reason we should not use any product, biologic or drug, in a species in which it has not been tested; especially wildlife species.With regards to contaminating agents within cell cultures the most common contaminating agent is one of the viruses, of greatest problem to the cattle industry a togavirus, called bovine virus diarrhea virus (BVDV). It is very difficult to maintain any cell lines free of that virus and, furthermore. It's even more difficult to detect the contaminating non-cytopathic BVD when it's present. A second common example of an adventitious agent is another group of viruses of concern to the veterinary community the Parvoviruses, particularly the porcine parvovirus which gets into tissue culture from contaminated trypsin. So yes, we must be ever aware of vaccine contaminants. We must also be aware of mycoplasma contamination and every other contaminant that can end up in cell culture that have product like fetal bovine serum and trypsin used on them.Siegl: We did a lot of work isolating porcine parvovirus out of cell cultures. We analyzed 43 cell cultures of different origin. From 38 of these cultures, we could isolate parvovirus. About 32 isolates were porcine parvovirus and some of the other were of rodent origin. For two viruses we don't yet know the natural host.Tizard: I think it's difficult to overestimate the importance of these contaminants. There an a number of examples of diseases being spread because of this.For instance, reticuloendotheliosis was introduced into Australia with Marek's disease vaccines for poultry. This problem, is intrinsic to modified live products and can be readily overcome through the use of inactivating agents.Swango: Yes, I agree, and certainly when we're at in the 1980s approaching 1990, we have technology that will greatly improve that. But I think Dr. Salk could take us back to the early days of that vaccine and inactivating agents did not inactivate a contaminant. Unless we know the contaminating agent is there to conduct surveillance on it, we cannot be assured that inactivation will inactivate all contaminating agents.Salk: Apropos of that, you're referring to the SV40 virus which was a contaminant in monkey kidney cell cultures. The last thing in the world that one would want to do now is to make vaccines out of the tissues of monkeys that come from the jungle. That was a learning experience you might say. At this point, we are much more sophisticated and can use continuously propagating cell lines, such as the Vero cell. The SV40 story alerts us how to avoid these things in the future.Schultz: One more comment is, if we don't know what the contaminating agent is or if it is introduced after inactivation has occurred, we still have the potential for the introduction of a live agent, even in an inactivated product. So we've come a long way, but we've got a tong way to go.Tizard: Except it's much more common, of course, using an inactivated product to add preservatives which will minimize that.Schultz: Nucleic acids are quite resistant to many of the inactivating agents or the preservative and the nucleic acid, the genetic material of the virus is often all that is necessary under certain sets of circumstances, to get infection in the vaccinate.Salk: This is free advice, You might just use some gamma rediation on the final product.Rude: What do you think the average veterinarian should know or be told about the advantages and disadvantages of modified live virus vaccines?Salk: There's one unique situation. That has to do with polio, because there's a choice. The argument is offered that the live virus vaccine is more advantageous from the public point of view and the killed virus vaccine from the individual point of view. I cannot make that kind of distinction because I know that with a killed virus vaccine one can control the disease effectively from both the public and individual point of view. If the physician, in this instance, were fully informed, he could make a choice because with the killed virus vaccine we can eliminate the disease altogether, both vaccine-induced and naturally-occurring disease. This unique situation is possible since we can provide a clear-cut choice.Swango: We have a difference in animal medicine compared to human medicine.Perhaps this could be illustrated best by some of our diagnostic procedures. In dealing with poultry flocks we've got sick birds. Instead of immediately trying to treat all the birds sometimes it is prudent to go ahead and euthanize some of those living birds so that we can get a more accurate, specific pathologic diagnosis. The same is true of swine. So we do have a difference here. With respect to what do we tell the veterinarian, let me suggest that we need to do everything we can to minimize risk to make products as safe and as effective as possible. However, I think the veterinarian or the animal owner should be aware that anytime a product is administered there is a risk be it biological or pharmaceutical. Schultz: I think that all of us here would probably go on record as saying that are would find useful and essential, both modified live and inactivated vaccines in veterinary medicine. At least I would hope that we would go on record as saying that because there are certain disease conditions for which there an no satisfactory inactivated vaccines currently available. I think that's an important point that the veterinary practitioner needs to understand. Both modified live and inactivated vaccines have a place in veterinary practice. To get back to the issue Dr. Salk brought up, if we have a choice and we truly have the same efficacy in both products, then I think that everyone at this table would opt for the inactivated vaccine because of the potential safety aspect: I don't think there is anyone here who would disagree with that.Rude: We're going to be talking about safety and I think it's been brought out that any biologic can create some problems in vaccinated animals.Schultz: I brought that out earlier. It you're going to put an exogenous agent, whether it be biologic or drug, into an animal, including humans, you've got to realize the potential danger, whether it's an aspirin you're going to take 10 minutes from now because you have a headache or whether it's an inactivated vaccine.Rude: We have been discussing modified live virus vaccines and also talked briefly about inactivated virus vaccines. Now I would like to discuss inactivated virus vaccines in more depth. What do you believe is the primary advantage associated with the use of inactivated virus vaccines?Swango: From my perspective the primary advantage would be and this is partly theoretical is safety; to minimize the risk of a live agent that could replicate and undergo these theoretical changes we have talked about. That would be the primary advantage.Schultz: We are talking in terms of inactivated viral vaccines and it might be important to point out again to the practitioner that we're probably talking about whole unit and sub-unit virus vaccines. We probably should also be talking about synthetic vaccines, so I think that the people know that inactivated only refers to whole virus and in veterinary medicine inactivated or killed viral vaccines are still just whole inactivated virus with which we've had some poor experiences. We also need to bring this to the level of current development. Are we, in this context, talking about sub-unit or synthetic or just whole inactivated product?Salk: Let's use the concept of non-infectious.Rude: That's a good term. Instead of saying 'inactivated,' we will use the term 'non-infectious' vaccinesSalk: Well, one has already been mentioned, its non-infectious character, reducing those risks that are associated with an infectious agent. Another advantage I see is the capacity to include immunogens for a large number of diseases at the same time, so as to reduce the number of vaccine administrations. This will be of increasing advantage in human medicine, and in veterinary medicine requiring the use of adjuvants as potentiating agents for that purpose. It allows the use of smaller quantities of the immunogen, producing more powerful and longer lasting effects.Siegl: When we are using non-infectious vaccines, we can have these vaccines highly controlled with respect to purity. We can purify them and take out as far as possible all material then might generate adverse effects.Tizard: The only other advantage could think of In addition to the primary one which is safety, is that commonly they're rather easier to store.Siegl: There's one additional advantage. Application of such a vaccine by chance to another species is not very likely to do any harm.Schultz: That raises an important point. We have had the idea for years that vaccines, if they don't do any good, won't cause harm. I think that's another concept the veterinarian has to get away from because whether it be modified live or non-infectious, there is the potential to cause harm! We've seen a good example of that within the last couple of year with some non-infectious products that were causing a great deal of harm, i.e. hypersensitivity reactions both generalized and systemic causing untoward disease namely immune mediated disease which we had never seen in that species prior to the introduction of a non-infectious vaccine.Rude: In the past, inactivated or as we now say, non-infectious, virsus vaccines have been criticized for inducing low levels of immunity of rather short duration in vaccinated animals. The early killed canine parvovirus vaccines were an example, How do the newer non-infectious virus vaccines perform in this regard?Tizard: I think that's a fair statement you just made, that indeed at least in veterinary medicine the non-infectious products have been poorer vaccines than the modified live ones. One of the reasons for our enthusiasm for modified live products has been that they have been somewhat better vaccines. In addition, of course, we have also needed to incorporate considerably more antigen is a non-infectious product than in a modified live product in order to get enough antigen into the dose and this had an adverse effect; on the price. Until we recognized that we had to enhance the immunogenicity of these non-living products. They were secondary products that could not compete with the modified living ones.Rude: When you talk about enhancing the immunogenicity of non-living products you are referring to adjuvants How Important are adjuvants in non-infectious virus vaccines?Tizard: They make a whole range of non-infectious, noninfectious living products possible that otherwise would not be possible. This is especially true as we move into genetically-engineered products, into sub-unit products, into synthetic products where relatively small quantities of relatively poorly antigenic material are used. As Dr. Salk pointed out, if you want to do better than nature you're going to have to add something to that product in order to get a superior immune response. An immune response that is at least of a size and duration similar to the currently available modified live virus vaccines. This all centers on the successful use of adjuvants.Siegl: I would like to raise two points. The first is that, with virology proceeding, we certainly have made progress towards production of more antigen at lower cost. I'm thinking of canine parvovirus vaccine where we can now grow the virus to high concentrations. This possibility has been denied before, when most laboratories failed to produce high concentrations of antigen in cell culture. From that time stems the difficulty of immunizing dogs with a killed or non-infectious parvovirus vaccine. The second point is in context with genetically engineered vaccines, sub-unit vaccines and so on. We now begin to understand how the immune system works. We know what antigenic determinants must be present to trigger the immune system at its various levels and there's a huge possibility for the future to produce good and effective non-infectious vaccines.Schultz: I think one of the things that the veterinary community is having problems with again, as it had problems with for years, is considering antibody responses to mean protective immunity. When we develop new, inactivated or non-infectious viruses and as we add new adjuvants the principle measure of immunity, unfortunately that the companies are using are antibody titers to the virus. Some or these titers are higher than we've ever seen before but the vaccines are no more efficacious against challenge with the disease organism than were the older, non-infectious products that didn't induce or induced a just detectable antibody response. So we have to be very careful that we understand the mechanism of protective immunity and realize it's not always evident by measuring an antibody titer. It veterinary biologic companies will keep that in mind and will slop using antibody titers as a marketing ploy which they have used for year to the veterinary practitioner, most of whom feel antibody titers an synonymous with protective immunity, we might better serve our clients and their animals.Salk: I think this deserves the attention that you're giving it. I have tried to determine what the correlates of immunity were. In the case of influenza. we found that it related to keep of antibody at the time of infection. The reason is that the portal of entry and of pathology in the same. That's where the block of infection has to occur. In the case of polio, the minimum requirement for immunity to disease, i.e., paralysis, is merely the presence of immunologic memory. We do not require persistence of detectable antibody. The presence of memory can be determined by giving a dose of vaccine and observing a maximum response within seven days.| In the case or polio a single effective dose can produce lifelong immunity because memory is durable. In the case of influenza you need two doses in order to induce the anamnestic response and in addition, you need an adjuvant. For polio, you don't. We've come a long way in understanding the mechanism of immunity, and therefore, how to design an immunogen to produce protection against clinical disease, i.e., protection against paralysis, be it paralysis of the immune system or paralysis of the central nervous system or wherever find of pathology it may be, hepatitis, etc. The immunogen needs to be formulated to produce the desired effect.Tizard: May I make a more general comment following this discussion an immunology? Veterinary vaccines, while remarkably successful in controlling disease, have had major areas of failure where they have not been impressively successful. The two I can think of are control of diarrhea diseases and the control of respiratory disease in large animals. Much of thin stems from our lack of knowledge about the things we were talking about earlier, In many cases, we succumbed to the ideas that the appearance of antibodies is sufficient to cause protection. Although there has been a tremendous growth of knowledge of the exact mechanism of defense in many respiratory and enteric diseases, until we know as much about them as we do about viruses such a distemper, we maybe are doomed to continue our unimpressive performance.Salk: Apropos of the remarks I made earlier about Influenza where there is a short incubation period, you don't have the advantage of the anamnestic effect after exposure as in the prevention against disease as with rabies, hepatitis, polio, measles, etc. For respiratory disease generally and enteric disease, became of portal of entry, you do have to have antibody at the portal of entry and at a higher level than you would for the other diseases because for respiratory and enteric disease the degree of immunity locally in proportional to the level of antibody. It would be possible to develop improved vaccines by the use of adjuvants a we've been able to show for influenza in humans. There are remedies. We need to understand the mechanisms and the differences to formulate the different vaccines.Rude: This rationale for the use of adjuvants is primarily to enhance antibody-mediated and cell-mediated immune responses. Would you give an explanation about what we mean by antibody-mediated immune responses and cell-mediated immune responses?Schultz: With regard to cellular immunity sometimes referred to as cell-mediated immunity, we have to include phagocytic processes with macrophages and T-cell cytotoxic lymphocyte responses. I would also include natural effect or natural cell-mediated cytotoxicity as cellular immunity and delayed type hypersensitivity. There is a transitional form of immunity called antibody dependent cell-mediated cytotoxicity (ADCC) that require both cells and antibody for protective immunity to disease. Then there is the classical humoral immunity in which antibody alone provides protection. It's important to understand that for certain viral agents and perhaps for most, both cellular and humoral immunity play a role in protection against clinical disease. However, to my knowledge, the only specific immune factor that can truly prevent infection with a virus is antibody. It's probably rare that we achieve that level of protection, but I just gave an example of it in canine distemper when. if you look at maternal antibody which in the only thing available to prevent infection is the antibody that's present as a result of transfer in the colostrum, then you get some ides of how important humoral or antibody-mediated protection is. That puppy with maternal antibody cannot be infected: is able to resist challenge with a particular agent. Distemper is an example where antibody alone will work to provide solid protection against infection.Rude: Dr. Salk, you've had experience with the polio virus in this regard. Would you like to comment?Salk: In polio, the immune response that's required is not the same. It's altogether humoral, and in fact, it is so efficient that all you need is the capacity to respond rapidly. The only individuals who become paralyzed are those who have a sluggish immune response to the intestinal component of their infection. The immune response, as evidenced by the appearance of antibody in the blood, is too late to prevent the viremia that occurs. The purpose of immunization is simply to accelerate the responsiveness sufficiently which can be done by inducing enough memory. In the case of influenza, as I mentioned earlier, memory is not enough. There you also need antibody for preventing the infection. With a disease like AIDS the virus may very well be intracellular at the time of infection. Here it maybe possible to protect against disease but not against infection. Here the cellular component may be important. Both cellular and humoral factors an necessary for certain diseases, of which AIDS is an example and tuberculosis and many other bacterial diseases and parasitic infestations as well. Consequently. the immunogens that are needed have to be designed appropriately in each case. In the care of bacterial disease, such a diphtheria or tetanus, the antitoxin alone is altogether sufficient. It is important for practitioners to understand these differences and in that way anticipate the limitations as well as opportunities of a given immunogen.Rude: Do you believe the development of new types of adjuvants, that further enhance both antibody-mediated and cell-mediated immune responses or cellular immunity is important?Salk: Yes, so far as adjuvants are concerned, some of them can produce immunopathic effects as well as beneficial effects. In the case of complete Freund's adjuvant (mineral oil plus non-infectious mycobacterium tuberculosis bacilli), for example, when combined with a central nervous system component (i.e. myelin basic protein), you can actually produce experimental allergic encephalomyelitis. If you were to use incomplete Freunds' adjuvant (mineral oil without non-Infectious mycobacterium tuberculosis bacilli), you could actually prevent the induction of allergic encephalomyelitis by immunizing the animal with incomplete Freund's adjuvant This in an Illustration of the need to be circumspect about the nature of the adjuvant that you employ so as see to enhance the beneficial as compared to the undesirable effect. It's for this reason that there's a great misunderstanding about the usefulness of Freund's adjuvants. Freund's incomplete adjuvant is very useful and does not cure the detrimental effects that can be associated with the use of Freund's complete adjuvant. We were able to show this with influenza vaccine some 35 years ago, The application of that principle can now be further studied by the development of adjuvants designed specifically to produce particular desire effects, depending on which class of antibody you want to produce and whether cell-mediated or humoral immunity. We're entering a new phase, a new science you might say, in the development and use of adjuvants. This, I predict, is the next breakthrough in the evolution of vaccinology. Schultz: I didn't mention anything about adjuvants when you asked the previous question, but just very briefly, to build on what Dr. Salk has indicated in veterinary medicine we're doing to have to be very careful about the adjuvants we use. There is currently a great fervor and desire to get into the addition of many cytokines which include both lymphokines and monokines, without really having any knowledge about their effect on the whole body system. We're adding such things as interleukins to vaccines without knowing what the interleukines are going to do to the animal and to the immune system and perhaps they may be generating immunologic diseases. We have to add a note of caution at this point. Since these adjuvants and these products are so poorly understood, we need to enter into using them with the hope of better understanding and if ,in fact, we don't have that understanding, we need to get the results from their use into the hands of the scientific community so we can better explore the potential effects that they might have on an immunogen and on the immune system.Tizard: And yet, the use of poorly understood adjuvants has a long end distinguished history in vaccinology. We've been using alum since the 1920s and are still not sure how it works. It's also fair to say that we've been very conservative is our use of adjuvants. To the best of my knowledge, alum is still the only adjuvant used in human vaccines. In veterinary medicine there are a few examples of saponin or DEAE dextrose being used.Schultz: Newer adjuvants are in use now in veterinary vaccines.Tizard: Yes, but in veterinary medicine the problems caused by adjuvants relate not only to safety and efficacy but also to contamination of meat and meat products.Siegl: I would say a complete new field is developing. At its scientific level there is an especially huge effort being made to understand how all these adjuvants are working and what is really the active substance. We might get away from using the old mycobacterial extract and go down to some few amino acid or peptides or phosphorylated peptides to see how these work. In addition, as far as I see it, there is a field developing on how you can apply these adjuvants in the best possible way, that they really produce the effect you like. For example, adding these adjuvants to the vaccines directly or blending them in might not be as beneficial as applying the adjuvant is the form of liposomes or something like that.Swango: Just a general comment about the adjuvants and where we're at. I think this certainly is a new ere that we're entering in which, in the next few years, we're going to see a lot of information being developed on how some of these factors are beginning to operate. The only additional comment is just to underscore what has been alluded to and stated here by Dr. Schultz and Tizard. In food animal medicine, we have to be very careful about residues of products in animals following vaccination, so we may be confronting a different problem in that facet of veterinary medicine than what we will be in companion animal medicine or human medicine.Rude: Earlier, when we were talking about modified live virus vaccines, we talked about virus shedding. Some of you mentioned there might be some benefits associated with shedding of modified live vaccine viruses from vaccinated animals. Would you characterize the lack of viral shedding as a disadvantage which might be associated with non-infectious vaccines when they are used to immunize a herd of cattle or a litter of puppies?Swango: With respect to canine parvo we have a unique situation in the passive immunity of that disease in which, as puppies are, losing their maternally derived antibody, they reach a point at which they become susceptible to infection with virulent virus earlier than what they can be immunized with vaccine, so we have a window of increased susceptibility but not immunizable and we have variation of titers within a litter. Everybody is not going to be on the same scale, so it isconceivable and in fact it has been demonstrated that on a given day we may have one individual in a group that can respond to vaccine, either killed or live. If we're using a live virus vaccine, that animal may be shedding the virus, depending on the vaccine that's been used a few days following vaccination at a time when its litter mates become susceptible or immunizable and hence, become infected and respond to that live virus vaccine. So, in essence, with certain live virus vaccines, one can immunize one individual and in turn immunize the entire group. whereas with the killed vaccine that cannot happen. Earlier, I think it was Dr. Schultz who said we needed to be careful in what we communicate to practicing veterinarians because we have gone through an era where there was a lot of promotional emphasis pointing out all the adverse effects of virus shedding from vaccinated animals lymphopenia. Most of these comments that had been perpetrated on our profession were not based on factual data. They were based on erroneous assumption. Canine parvovirusis not immuno-suppressive, period, even though virulent virus, in certain vaccines, do cause lymphopenia following vaccination. It is not immuno-suppressive. Shedding of the vaccine virus from canine parvovirus has not been demonstrated by anyone with definitive data to cause a problem and, therefore a lot of the promotional emphasis stressing lack of shedding of virus lack oflymphopenia, or in one or two cases, killed vaccine, was off base. It only generated a lot of fear response among dog owners as well as veterinarians about the use of these vaccines. That's one advantage to a live virus vaccine in the case.Tizard: While what Dr. Swango is saying almost certainly true, it is also in sense anti-scientific to simply put an a virulent strain into a population and hope that by doing this it will transmit to the unprotected individuals. I would have thought that it would be much more appropriate to use a slightly different technology such as a slow release vaccine to in fact, ensure that animals get protected in a more formal and organized manner.Swango: I agree with Dr. Tizard team the standpoint of approaching a better solution to a problem, but when we've got a dog developing a parvovirus disease. we cannot wait for our scientists develop a slow release product..Tizard: I support that.Salk: There are two things I'd like to comment on. One has to do with the herd effect as I understood it. To me, it means that if you immunize a fraction of the population that the rest of the population will be protected. Vaccinating a segment of the population protests the unvaccinated segment, Is that true?Tizard: Yes. That's true.Salk: We have shown that in influenza and in polio. That's what I mean by herd effect..Swango: We can show you that for rabies control as well in animals.Salk: I don't doubt that. You reduce the number of disseminator and therefore the potential recipients are protected. For every disease there is a threshold beyond which you need not go to have a desired effect. That's one way of dealing with the problem that you were referring to. You don't have to shed virus in order to produce a herd effect. That's not what I understand to be the herd effect. That is spreading by shedding. We have used incomplete Freund's adjuvant to protect antigens from maternal anti-body.Schultz: I'll use canine parvovirus in this specific example. We've been working on the problem of overcoming maternal immunity to a variety of agents to about 15 years now and with regard to canine parvovirus specifically we have used incomplete Freund's adjuvant. We are using liposomes 'with both intact virions and make DNA. We have also used viral vectored vaccines. I can categorically state that Incomplete Freund's adjuvants and other adjuvants will not overcome this suppression by maternal immunity to canine parvovirus Even when we give incomplete or complete Feund's adjuvant with Vaccine to animals that we would consider to be just at the border of being susceptible to immunization (maternal antibody is very low) in our hands that happens to be about 1:40 HI titer canine parvovirus adjuvant will not make the vaccine immunize I don't know why the addition of adjuvant will not work but we can show that just by increasing the antigenic mass we can overcome a 1:40 maternal titer. I'd like to go on record that we have not found any commercial canine parvovirus vaccine that will overcome maternal immunity even at levels as low as I:40 to 1:80 titer. So we're dealing in canine parvovirus disease with this "window of vulnerability" where the puppy becomes susceptible to infection with virulent virus two to four weeks before the current vaccines are able to actively immunize which may not be until 16, I8 or 20 weeks. The only way that I know of overcoming that problem will be by increasing the antigenic mass in the vaccine not by adding an adjuvant.Salk: You cannot possibly do magic by the use of an adjuvant unless the amount of antigen is adequate, so that is clear. The other point I was going to raise was whether or not the immunogen is a carbohydrate immunogen because, under those circumstances there is delay.Schultz: No. this is a protein.Rude: I have always believed, a Dr. Salk has mentioned, that an adjuvant, such as Freund's incomplete adjuvant. protects a non-infections virus from being neutralized by maternal antibodies. I have also believed that the slow release of a non-infectious virus from an adjuvant depot may induce an active immune response if maternal anti-bodies have decreased to non-protective levels. Based on what you have stated. Dr. Schultz, this does not happen?Schultz: In practice it does not happen. The vaccines that we currently have available with adjuvants do not immunize animals with maternal antibody more effectively than the modified live vaccines on the market. The reason for the inability of the inactivated vaccines to immunize are not clear but may relate to the adjuvant being used or the lack of an adequate antigenic mass. Thus, although your statement is theoretically correct, field experience wouldsuggest that adjuvanted non-infectious vaccines do not effectively immunize animals with maternal immunity. Likewise, we're not seeing an anamnestic response from most modified live or non-infectious products. So this yearly vaccination, for example, for distemper, cause an anamnestic response in less than 1 percent of vaccinated dogs.Rude: If a non-infectious virus vaccine is used for the initial vaccination, should animals be revaccinated with a non-infectious or modified live virus vaccine, or dose it matter?Tizard: It doesn't matter but the USDA license is issued for a matched set of vaccines.Siegl: Several concepts have been developed which call for revaccination with a modified live vaccine. In my opinion, this is nothing but a compromise to come to meet both the adherents of non-infectious and of live vaccines. Personally. I can see no need for using modified live virus for the revaccination and, anyway. I favor the use of non-infectious vaccines whenever possible.Schultz: If an animal is vaccinated with a non-infectious vaccine it should, if necessary, be revaccinated with a non-infectious vaccine, since the immune response from the original vaccination would likely interfere with a modified live vaccine. For the most effective immunity when modified live vaccines and non-infectious products are used in the vaccination programs the modified live vaccine should be used fist, followed by the non-infectious vaccine. This is done for two reasons. First, the modified live vaccine usually provides more effective and complete immunity, and secondly, the non-infectious vaccine is more likely to provide an anamnestic response. Non-infectious vaccine fail to stimulate certain aspects of cellular and local immunity, therefore, if the modified live vaccine is used first, these forms of immunity will present to protect against disease."If a non-infectious virus vaccine is used for the initial vaccination, should animals be revaccinated with a non-infectious or modified live virus vaccine?" Dr. Ted Rude"We're entering a new phase, a new science, you might say, in the development and use of adjuvants. This, I predict, is the next breakthrough in the evolution of vaccinology. " Dr. Jonas Salk"Both modified live and inactivated vaccines have a in a veterinary practice... if we have a choice, and we truly have the same efficacy in both products, I think everyone at this table would opt for the inactivated vaccine because of the potential safety aspect."Dr. Ron Schultz" We now begin to understand how the immune system works. We know that antigenic determinants must be present to trigger the immune system at its various levels and there's a huge possibility for the future to produce good and effective, non- infectious vaccines." Dr. Gunter SieglWe somehow need to redirect emphasis that just because we vaccinate, we cannot ensure immunity, There is a difference between vaccination immunization. Dr. Larry Swango"'While we certainly have to give credit to modified live veterinary vaccines for having had a tremendous impact in controlling disease in this country, they do represent a fairly basic technology that can be improved upon." Dr. Tizard

Christine.

Dr Macluggage talking about it here

This article originally appeared in the Journal of American Holistic Veterinary Medical Association, May - July, 1995, Vol. 14, No. 2, Page 7

The San Diego Veterinary Medical Society held a two day symposium May 6-7, 1995 titled New Faces of Immune Mediated Diseases and Current Concepts in Vaccine Immunology. The first day was devoted to immune mediated diseases, and the second day dealt exclusively with vaccinations in companion animals.
Fred W. Scott, D.V.M., Ph.D., Cornell University, emphasized feline diseases and vaccinations. Ronald D. Schultz, Ph.D., University of Wisconsin, covered canine immune mediated diseases and vaccinations. David M. McCluggage, D.V.M., Chapparal Animal Health Center, Boulder, Colorado presented the holistic perspective on vaccinations.
All three speakers agreed that there is no justification for current recommendations that emphasize the need for annual vaccinations.
Dr. Scott indicated that until more data is available, veterinarians could safely recommend revaccinating for rabies every three years, and feline panleukopenia could be given every three, five or even every seven years. He did indicate that feline panleukopenia is an exceptionally effective vaccine, providing excellent immunity. He has a specific pathogen free (SPF) group of cats in which he has been following titers for feline panleukopenia, feline herpesvirus (Rhino tracheitis), and feline calicivirus. It is particularly significant that he is testing persistency of titers in SPF cats, because there is no exposure to natural infections which would boost titers following vaccination. He has seen protective titers for feline panleukopenia in 100% of the cats he has tested for four years following vaccination (they have not been re-vaccinated in that period of time). Feline herpesvirus has shown protective titers in 100% of the cats as well. Feline calicivirus showed protective titers in 60% of the cats tested. It is interesting to note that titers actually increased slightly between the third year and the fourth year for calicivirus, although the percent of cats showing protective titers did not increase between the two years. The study is ongoing and he will continue to collect data on the cats in future years.
Dr. Scott also covered feline leukemia virus vaccines. Although most feline leukemia virus vaccines are not particularly effective, he did mention two that provided good protective titers in tested cats. They were Fel-O-Vac, Ft. Dodge Laboratories, and Fevaxyn-FeLV, Solvay Animal Health. Both showed what he termed a protective factor of 91%. He also emphasized that to control FeLV, testing and isolation of affected cats (not vaccinating) was the key factor. FeLV incidence has decreased since the introduction of the vaccines, but he could not say if that was due to vaccination or testing and isolating FeLV positive cats.
Dr. Schultz believes that the only significant disease in dogs today is canine parvovirus. All the other diseases we vaccinate for have either decreased in incidence to fairly insignificant levels, do not provide good protection or have had no place in canine vaccine protocols from the beginning for various other reasons. Killed virus vaccines are not as effective. Only high titer modified live virus parvovirus vaccines are capable of breaking through the lingering maternal immunity. He emphasized that between the time the maternal immunity begins to wane and when most parvovirus vaccines are capable of providing immunity can often be as long as 10-15 weeks. Maternal immunity often begins to wane at about five to six weeks, and the pups become susceptible to the disease. Even in the face of vaccinating with most parvovirus vaccines, the pup remains susceptible until about 16-22 weeks. This is the reason many vaccinated puppies develop clinical infections. After 22 weeks almost any vaccine can provide immunity, but by that time, the dog's immune system is strong enough to fight off the infection. Due to maternal antibodies blocking the development of vaccine induced immunity, it becomes critical to only use the high titer parvovirus vaccines. They are capable of breaking through the maternal immunity block and protect the pup. His favorite parvovirus vaccine is lntervet's Progard, and he also believes that Fort Dodge's Durammune is a good vaccine.
He does not particularly advocate the use of canine vaccines other than rabies and canine distemper. In specific situations where there is a risk of high exposure, he might recommend certain other vaccines. Canine distemper is almost never seen any more, so the need to vaccinate for it is small. Because of the severity of canine distemper, he still recommends vaccination. For legal and public health he advocates vaccinating for rabies.
A minimal vaccine protocol for veterinarians, according to Dr. Schultz, might be a monovalent parvovirus vaccine at about 8-10 weeks and repeated again at 12-14 weeks. He also recommended a monovalent canine distemper vaccine at 6-8 and again at 14-16 weeks. Rabies vaccine should be at about 12 weeks of age. He did not see the need to vaccinate for any of these diseases after the initial vaccine, unless the parvovirus vaccine used earlier was not one of the two he recommended. Then he would recommend a single dose of one of the two parvovirus vaccines previously mentioned. If the dog was older than 22 weeks, even if one of the less effective vaccines were used, he did not necessarily recommend re-vaccinating with one of the two high titer vaccines.
Since canine distemper does not come as a monovalent vaccines, Dr. Schultz said that it would be acceptable to vaccinate twice with canine distemper/measles vaccine. Dr. Schultz was not particularly impressed with the need to vaccinate routinely with any of the other canine vaccines that are available. Animals known to have higher exposure to one of the several other diseases that have vaccines available could receive vaccination for those diseases. He gave minimal vaccine protocols for these vaccines as well. He mentioned that leptospirosis is the vaccine that most commonly leads to anaphylaxis, and all of the leptospirosis cases that the University of Wisconsin has seen in the last few years was not due to the Leptospirosis strains present in the vaccines.
Dr. Schultz discussed modified live versus killed vaccines, and believes that some MLV vaccines are necessary (eg. parvovirus) and should be used. At other times killed vaccines (eg. rabies) should be used when they are effective. He did not agree with the general view that killed vaccines are always preferable to MLV vaccines, because the first criteria for a vaccine is that is effective and provides immunity. Also, killed vaccines do contain a much higher level of virus particles. Sometimes the immune response killed vaccines produce lead to immunopathological disease at time of infection rather than protection.
Dr. Schultz stated that there is no reason to vaccinate companion animals on an annual basis, unless it is used as a method to bring animals in for yearly exams.
As a general rule, Dr. Schultz would prefer all vaccines be available as monovalent vaccines to allow for an individualized approach to vaccination. But, he does not see any scientific evidence that any of the currently available polyvalent vaccines are causing any problems with vaccine interference or immunosuppression.
Both Dr. Schultz and Dr. Scott believe that the killed rabies vaccines on the market provide good protection for the three year duration for which they are licensed, and probably far longer.
Dr. McCluggage covered the holistic perspective on vaccinations. He stated that veterinarians must re-educate the public about the importance of vaccinations as a method of maintaining their companion animal's health. He pointed out that there is good epidemiological evidence that most of the major diseases of man that are being vaccinate for declined primarily due to reasons other than vaccination. Vaccines are certainly effective at times, but can never be expected to be as significant as good nutrition, proper sanitation and isolation of affected people or animals. Testing for diseases and isolation of carrier animals is far more effective than vaccination.
He stated that we must stop advocating yearly vaccines because of the harm we are doing to the animals we vaccinate. He covered the homeopathic concept of "vaccinosis". Vaccinosis is a disease entity that may be introduced through vaccinating animals or people. Once vaccinosis develops, there is a disturbance in the bodies vital forces that leads to symptoms of chronic disease that can be very difficult (and often impossible) to cure.
Dr. McCluggage also stated that veterinarians should not vaccinate for diseases that have little mortality. Natural immunity provides far better immunity. Diseases that only produce morbidity should not be vaccinated for, due to the risk of vaccinosis and the allopathically recognized side effects such as immune mediated diseases and anaphylaxis.
Dr. McCluggage recommended that animals receive a vaccine protocol similar to Dr. Schultz's minimal vaccine protocol mentioned above, and that no boosters be repeated after the first series. He stated that there are no good reasons to recommend annual vaccinations for our companion animals. For clients Interested in a holistic approach, nosodes should be employed instead. Dr. McCluggage discussed alternative methods to run a profitable veterinary practice, including utilizing alternative modalities such as acupuncture and chiropractic medicine. He also pointed out that veterinarians can distinguish themselves from low cost clinics and vaccination clinics by advocating high quality individualized medical care.
By the end of the symposium it was clear that all of the speakers agreed that animals are over-vaccinated today. A new approach is needed or the general public will tend to lose confidence and the high degree of respect veterinary medicine currently enjoys.

Christine.

I think I'll print those out for reading later

More from Dr Dodds

Vaccine Protocols
for Dogs
Predisposed to
Vaccine Reactions
W Jean Dodds DVM
DrJean Dodds is the woman who first told the truth
about vaccines to dog lovers. A member of the scientific
community, Dr Dodds clearly felt that dog owners had a right
to know the truth so that they could make informed and wise
decisions. We all owe Dr Dodds a huge, enormous, debt of
gratitude. The following paper was published in the Journal
of the American Animal Hospital Association (37: 1-4, 2001).
There is increasing evidence in veterinary medicine that
vaccines can trigger immune-mediated and other chronic
disorders (i.e., vaccinosis), especially in certain apparently
predisposed breeds (1-6). Accordingly, clinicians need to be
aware of this potential and offer alternative approaches for
preventing infectious diseases in these animals. Such
alternatives to current vaccine practices include: measuring
serum antibody titers; avoidance of unnecessary vaccines or
overvaccinating; and using caution in vaccinating ill, geriatric,
debilitated or febrile individuals, and animals from breeds or
families known to be at increased risk for immunologica!
reactions (3,5-. __________________
Adverse Effects of Vaccines
As the most commonly recognised adverse effect of
vaccination is an immediate hypersensitivity or anaphylactic
reaction, practitioners are less familiar with the more rare but
equally serious acute or chronic immune-mediated
syndromes that can occur. The veterinary profession and
vaccine industry have traditionally emphasised the
importance of giving a series of vaccinations to young
animals to prevent infectious diseases, to the extent that this
practice is considered routine and is generally safe for the
majority of animals. Few clinicians are prepared, therefore,
for encountering an adverse event and may overlook or even
deny the possibility.
Beyond the immediate hypersensitivity reactions, other
acute events tend to occur 24 to 72 hours afterward, or 7 to
45 days later in a delayed type immunological response
(1,6,9,10). Even more delayed adverse effects include
mortality from high-titered measles vaccine in infants, canine
distemper antibodies in joint diseases of dogs, and feline
injection-site fibrosarcomas (3,11). The increasing antigenic
load presented to the host individual by modified-live virus
(MLV) vaccines is presumed to be responsible for the
immunologica) challenge that can result in a delayed
hypersensitivity reaction (6,9).
The clinical signs associated with nonanaphylactic
vaccine reactions typically include fever, stiffness, sore joints
and abdominal tenderness, susceptibility to infections,
neurological disorders and
encephalitis, autoimmune hemolytic
anaemia (AIHA) resulting in icterus, or
immune-mediated thrombocytopenia
(ITP) resulting in petechiae and
ecchymotic haemorrhage (1-4,9,10,
12,15). Hepatic enzymes may be
m a r k e d l y elevated, and liver or kidney failure may occur by itself or
accompany bone-marrow suppression
(3). Furthermore, MLV vaccination
associated with the
development of transient seizures in
puppies and adult dogs of breeds or
crossbreeds susceptible to immunediseases,
especially those
involving haematological or endocrine
tissues (e.g., AIHA, ITP, autoimmune
thyroiditis) (1-3). Postvaccinal
polyneuropathy is a recognised entity
associated occasionally with the use
. of distemper, parvovirus, rabies and
possibly other vaccines'(3,6,9). This
can result in various clinical signs,
including muscular atrophy, inhibition
or interruption of neuronal control of
tissue and organ function, incoordination,
and weakness (3).
Therefore, we have the responsibility
to advise companion animal breeders and caregivers of the
potential for genetically susceptible litter mates and relatives
that are at increased risk for similar adverse vaccine
reactions (1-5).
Commercial vaccines, on rare occasion, can also be
contaminated with other adventitious viral agents (6,16)
which can produce significant untoward effects such as
occurred when a commercial canine parvovirus vaccine was
contaminated by blue tongue virus. It produced abortion and
death when given to pregnant dogs (16) and was linked
casually to the ill-advised but all-too-common practice of
vaccinating pregnant animals. The potential for side
effects such as promotion of chronic disease sites in
male and non pregnant female dogs receiving this lot of
vaccine remains in question, although there have been
anecdotal reports of reduced stamina and renal
dysfunction in performance sled dogs (3). Recently, a
vaccine manufacturer had to recall all biological products
containing a distemper component, because they were
associated with a higher-than-expected rate of central
nervous system Postvaccinal reactions 1 to 2 weeks
following administration (3).
If, as a profession, we conclude that we are
overvaccinating, other issues come to bare, such as the
needless client dollars spent on vaccines, despite the
well-intentioned solicitation of clients to encourage annual
booster vaccinations so that pets also can receive a
wellness examination (5). Giving annual boosters when
they are not necessary has the client paying for a
service which is likely to be of little benefit to the pet's
existing level of protection against these infectious
diseases. It also increases the risk of adverse
reactions from the repeated exposure to foreign
substances.
Polyvalent MLV vaccines, which multiply in the host,
elicit a stronger antigenic challenge to the animal and
should mount a more effective and sustained immune
response (5,6,9). However, this can overwhelm the
immunocompromised or even healthy host that has
ongoing exposure to other environmental stimuli as well
as a genetic predisposition that promotes adverse
response to viral challenge (1-3,9,13). The recently
weaned young puppy or kitten being placed in a new
environment may be at particular risk. Furthermore, while
the frequency of vaccinations is usually spaced 2 to 3
weeks apart, some veterinarians have advocated
vaccination once a week in stressful situations. This
practice makes little sense, scientifically or medically (5).
An augmented immune response to vaccination is
seen in dogs with pre-existing inhalant allergies (i.e.,
atopy) to pollens (3). Furthermore, the increasing current
problems with allergic and immunological diseases have
been linked to the introduction of MLV vaccines more than
20 years ago (6). While other environmental factors no
doubt have a contributing role, the introduction of these
vaccine antigens and their environmental shedding may
provide the final insult that exceeds the immunological
tolerance threshold of some individuals in the pet
population.
Predisposed Breeds
Twenty years ago, this author began studying families
of dogs with an apparent increased frequency of
immune-mediated haematological disease (i.e., AIHA,
ITP, or both) (12). Among the more commonly
recognised predisposed breeds were the Akita, American
Cocker Spaniel, German Shepherd Dog, Golden
Retriever, Irish Setter, Great Dane, Kerry Blue Terrier and
all Dachshund and Poodle varieties; but predisposition
was found especially in the Standard Poodle, Long-Haired
Dachshund, Old English Sheepdog, Scottish Terrier,
Shetland Sheepdog, Shih Tzu, Vizsia, and Weimaraner,
as well as breeds of white or predominantly white coat
colour or with coat colour dilution (e.g., blue and fawn
Doberman Pinschers, the merle Collie, Australian
Shepherd, Shetland Sheepdog, and harlequin Great
Dane) (1-3). Recently, other investigators have noted the
relatively high frequency of AIHA, ITP or both in American
Cocker Spaniels (10) and Old English Sheepdogs (13).
A significant proportion of these animals had been
vaccinated with monovalent or polyvalent vaccines within
the 30-45 day period prior to the onset of their
autoimmune disease (1,2,10). Furthermore, the same
breeds listed above appear to be more susceptible to
other adverse vaccine reactions, particularly Postvaccinal
seizures, high fevers, and painful episodes of
hypertrophic ostedystrophy (HOD) (3). For animals that
have experienced an adverse vaccine reaction, the
recommendation is often to refrain from vaccinating these
animals until at least after puberty, and instead to
measure serological antibody titers against the various
diseases for which vaccination has been given. This
recommendation raises an issue with the legal
requirement for rabies vaccination. As rabies vaccines
are strongly immunogenic and are known to elicit adverse
neurological reaction (3,5) it would be advisable to
postpone rabies vaccination for such cases. A letter from
the primary care veterinarian stating the reason for
requesting a waiver of rabies vaccination for puppies or
adults with documented serious adverse vaccine
reactions should suffice.
As further examples, findings from the author's large
accumulated database of three susceptible breeds are
summarised below._____________________
Vaccine-Associated Disease in Old English
Sheepdogs.
Old English Sheepdogs appear to be predisposed to
a variety of autoimmune diseases (1-3,13). Of these, the
most commonly seen are AIHA, ITP, thyroiditis, and
Addison's disease (2,17). Between 1980 and 1990, this
author studied 162 cases of immune-mediated
haematological diseases in this breed. One-hundred
twenty-nine of these cases had AIHA, ITP, or both as a
feature of their disease. Vaccination within the previous
30 days was the only identified triggering event in seven
cases and was an apparent contributing factor in another
1 1 5 cases (2). Thyroid disease was recognised as either
aprimary or secondary problem in 71 cases, which is likely
an underestimate of the true incidence, as thyroid function
tests were not run or were inconclusive in most of the
other cases.
Experience with a particular Old English Sheepdog
family supported a genetic predisposition to autoimmune
thyroiditis, Addison's disease, and AIHA or ITP or both -
an example of the polyglandular autoimmune (2,17).
Pedigrees were available from 108 of the 162 Old English
Sheepdog cases of autoimmune disease; a close
relationship was found among all but seven of the
affected dogs (2). Two of three pedigrees available from the
studies of Day and Penhale (13) were also related to this
large North American study group.
Vaccine-Associated Disease in Young Akitas
Akitas are also subject to a variety of immun-mediated
disorders, including Vogt-Koyanagi-Harada syndrome (VKH),
pemphigus, and heritable juvenile-onset immune-mediated
polyarthritis (IMPA) (3,14). Juvenile-onset IMPA occurs in
Akitas less than 8 months of age. Of 11 closely related
puppies in the author's case series, the mean age of onset
was 14 weeks (3). Initial signs appeared 3 to 29 days
following vaccination with polyvalent MLV or killed virus or
both, with a mean reaction time of 14 days. All had profound
joint pain and cyclic febrile illness lasting 24 to 48 hours.
Hemograms revealed mild non regenerative anaemia,
neutrophilic leukocytosis, and occasional thrombocytopenia.
Joint aspiration and radiography indicated nonseptic,
nonerosive arthritis. Despite treatment for immune-mediated
disease and pyrexia, all eight dogs had relapsing illness and
died or were euthanized by 2 years of age from progressive
systemic amyloidosis and renal failure. Necropsies were
performed on three dogs, two of which had glomerular
amyloiosis and wide spread evidence of vasculitis. The
history, signs and close association with immunisation
suggested that juvenile-onset polyarthritis and subsequent
amyloidosis in these Akitas may have been an autoimmune
response triggered by the viral antigens or other components
of vaccines (3).
The vaccine-related history was reviewed for 129
puppies belonging to the family of Akitas discussed above.
Polyvalent MLV vaccine was given to 104 of them, with 10
(9.8%) puppies showing adverse reactions and death.
Another six puppies received a polyvalent all-killed vaccine
product (no longer commercially available) with no reactors,
and 19 puppies received homeopathic nosodes initially
followed by killed canine parvovirus (CPV) vaccine, with one
reactor (5.6% that died, and one that became ill but survived
(3).
A genetic basis for immune-mediated disease and
immunodeficiencies states is well known
(1,2,12,13,15,17,1. The mechanism for triggering
immune-mediated disease is poorly understood, but
predisposing factors have been implicated when genetically
susceptible individuals encounter environmental agents that
induce non-specific inflammation, molecular mimicry, or both
(3,17). The combined effects of these genetic and
environmental factors override normal self-tolerance and are
usually mediated by T-cell imbalance or dysregulation (17).
Since the modem Akita arose from a relatively small
gene pool, understanding the potential environmental
triggers of juvenile-onset IMPA has immediate importance.
Numerous agents have been implicated, including drugs,
vaccines, viruses, bacteria, chemicals and other toxins (1-3,
10,11). Although litter mates from affected families typically
end up in different locales, all undergo relatively
standardised immunisation procedures at a similar age.
Vaccine-Associated Disease in Young Weimaraners
The Weimaraner breed appears to be especially
prone to both immune deficiency and autoimmune
diseases, which have been recognised with increasing
frequency in related members of the breed over the past 15
years (3). Autoimmune thyroiditis leading to clinically
expressed hypothyroidism is probably the most common of
these disorders, along with vaccine-associated HOD of
young Weimaraners (2,3,17).
During a 2-year period (1986-198, Couto (3) evaluated
170 related Weimaraners, including affected puppies and
their relatives. Clinical signs of the affected dogs included
high fevers, polyarthritis with pain and swelling typical of
HOD, coughing and respiratory distress from pneumonia,
enlarged lymph nodes, diarrhoea, pyderma, and mouth
ulcers. In most cases, clinical signs were first detected
shortly after vaccination with a second dose of polyvalent
MLV vaccine when the puppies were between 2 and 5
months of age. This author has studied more than 60
Weimaraners with vaccine-associated disease. In the 24
cases described in a previous article (3), the mean age of
onset of clinical signs was 13.5 weeks, with a mean reaction
time of 10.5 days post vaccination. Males were
predominantly affected. All affected puppies showed
high-spiking fevers, cyclic episodes of pain, and polyarthritis
(HOD) - a group of signs identical to those of the affected
young Akitas described previously. Most affected puppies
also showed leukocytosis (with neutrophilia or neutropenia),
diarrhoea, lethargy, anorexia, and enlarged lymph nodes.
Some puppies also had levels of immunoglobulin A,
immunoglobulin M, or both below those expected for their
age, and one puppy had immunoglobulin G (IgG) deficiency
as well. Other signs included coughing, pneumonia,
depression, deizures or 'spaced out' behaviour, refusal to
stand or move, and hyperesthesia ('walking on eggshells').
The outcome for half of these cases was good (12 of the 24
are healthy adults), although two died, three were euthanized
as puppies, and three remained chronically ill as adults.
Another four cases were lost to follow-up.
Management of this clinical syndrome is best
accomplished with an initial dose of parenteral
corticosteroids followed by a tapering course of
corticosteroids over 4 to 6 weeks. Systemic broad-spectrum
antibiotics may be given prophylactically, and vitamin C (500
to 1000 mg daily) can be included to promote immune
support. Recurring episodes are treated by increasing the
corticosteroid dosage for a few days until the flare-up has
subsided. The response to initial corticosteroid treatment is
always dramatic, with fever and joint pain usually subsiding
within a matter of hours.
Serological titers for canine distemper virus (CDV) and
CPV were determined in 19 of the 24 affected Weimaraner
puppies, and all were adequate. Upon reaching adulthood,
serum antibody titers were reevaluated and detectable CDVand
CPV-specific IgG persisted. Several of these dogs have
subsequently developed hypothyroidism and are receiving
thyroid replacement (3,4,17). Thus, to avoid recurrence of
adverse effects, which has been shown to be even more
severe if another vaccine booster is given, serological titers
for CDV and CPV are measured (7).
4 Another approach recommended by Weimaraner
breeders and this author is to modify the vaccination
protocol, especially for puppies from families known to
have experienced adverse vaccine reactions. Examples
would be to limit the number of antigens used in the
vaccine series to those infectious agents of most clinical
concern (i.e., CDV, CPV, and rabies virus), separating
these and other antigens to 2- to 3-week intervals, and
giving rabies vaccine by itself at 6 months of age. A
booster series is administered at 1 year by separating the
CDV, CPV, rabies virus, and other vaccine components,
where possible, and giving them on separate visits at
least 2 weeks apart. Thereafter, serological antibody
titers can be measured (except for those vaccines
required by law, unless a specific exemption is made on
an individual case basis). ___________
Recommendations
Practitioners should be encouraged during the initial
visit with a new puppy owner or breeder to review current
information about the breed's known congenital and
heritable traits. Several databases, veterinary textbooks,
and review articles contain the relevant information to
assist here (2). For those breeds at increased risk, the
potential for adverse reactions to routine vaccinations
should be discussed as part of this wellness program.
Because breeders of at-risk breeds have likely alerted the
new puppy buyer to this possibility, we should be mindful
and respectful of their viewpoint, which may be more
informed than ours about a specific breed or family issue.
To ignore or dismiss these issues can jeopardise the
client-patient relationship and result in the client going
elsewhere for veterinary services or even turning away
from seeking professional care for these preventive health
measures. As a minimum, if we are unaware of the
particular concern expressed, we can research the matter
or ask the client for any relevant scientific or medical
documentation. The accumulated evidence indicates that
vaccination protocols should no longer be considered as a
"one size fits all' program.
For these special cases, appropriate alternatives to
current vaccine practices include: measuring serum
antibody titers; avoidance of unnecessary vaccines or
overvaccinating; using caution in vaccinating sick, very
old, debilitated, or febrile individuals; and tailoring a
specific minimal vaccination protocol for dogs of breeds or
families known to be at increased risk for adverse
reactions (3,5-. Considerations include starting the
vaccination series later, such as at 9 or 10 weeks of age,
when the immune system is more able to handle antigenic
challenge; alerting the caregiver to pay particular attention
to the puppy's behaviour and overall health after the
second or subsequent boosters; and avoiding
revaccination of individuals already experiencing a
significant adverse event. Litter mates of affected
puppies should be closely monitored after receiving
additional vaccines in a puppy series, as they, too, are at
higher risk. Altering the puppy vaccination protocol, as
suggested above for the Weimaraner, is also advisable.
Following these recommendations may be a prudent
way for our profession to balance the need for individual
patient disease prevention with the age-old physician's
adage, forwarded by Hippocrates, of 'to help, or at least
do no harm'.
References
1. Dodds WJ. Immune-mediated diseases of the blood. Adv Vet Sci Comp
Med1983;27; 163-196.
2. Dodds WJ. Estimating disease prevalence with health surveys and
genetic screening. Adv Vet Sci Comp Med 1995,39:29-96.
3. Dodds WJ. More bumps on the vaccine road. Adv Vet Med
1999;41:715-732.
4. Hogenesch H, Azcona-Olivera J, Scott-Moncrieff C, Snyder PW,
Glickman LT. Vaccine-induced autoimmunity in the dog. Adv Vet Med
1999,41:733-744.
5. Schultz R. Current and future canine and feline vaccination programs. Vet
Med 1998:93:233-254.
6. Tizard 1. Risks associated with use of live vaccines. J Am Vet Med Assoc
1990;196:1851-1858.
7. Twark L, Dodds WJ. Clinical use of serum parvovirus and distemper virus
antibody liters for determining revaccinatton strategies in healthy dogs. J Am Vet Med
Assoc 2000;217:1021-1024.
8. Tizard I, Ni Y. Use of serologic testing to assess immune status of
companion animals. J Am Vet Med Assoc 1998:213:54-60.
9. Phillips TR. Jensen JL. Rubino MJ, Yang WC. Schultz RD. Effects of
vaccines on the canine immune system. Can J Vet Res 1989.53:154-160.
10. Duvai D, Giger U. Vaccine-associated immune-mediated hemolytic
anaemia in the dog. J Vet Intern Med 1996,10:290-295.

Some more

Vaccine-Induced Autoimmunity in the Dog
Advances in Veterinary Medicine Vol 41, pp 733-747
HARM HOGENESCH, JUAN AZCONA-OLIVERA, CATHARINE SCOTT-MONCRIEFF, PAUL W. SNYDER, AND LARRY T. GLICKMANDepartments of Veterinary Pathobiology and Veterinary Clinical Sciences, Purdue University, West Lafayette, Indiana 47907
I. IntroductionII. Materials and Methods A. Animals B. Vaccination Schedule C. Viral Serology D. Hematology E. Endocrinology F. Immunology G. Lymphocyte Blastogenosis Assay H. Enzyme-Linked Immunosorbent Assay (ELISA) I. Necropsy J. Statistical AnalysisIII. Results A. Viral Serology B. Clinical Observations, Hematology, and Endocrinology C. Immunology D. NecropsyIV. Discussion Acknowledgements References
I. Introduction Vaccines are widely used in human and veterinary medicine as an effective and economic method to control viral and bacterial diseases. Although generally considered safe, vaccination is occasionally accompanied by adverse affects. Many adverse affects related to vaccination are acute and transient, for example, fever, swelling at the site of the inoculation, and allergic reactions. In contrast, reports of autoimmune disease following vaccination are relatively rare. In most instances, it is difficult, if not impossible, to ascertain that vaccination caused or precipitated the autoimmune disease. In a recent report, the Advisory Committee on Immunization Practices in people concluded that there is a causal relation between diptheria-tetanus-pertussis (DTP) and measles-mumps-rubella (MMR) vaccination and arthritis, but no evidence of a causal relationship between these vaccinations and other autoimmune diseases such as autoimmune hemolytic anemia and Guillain-Barre syndrome (Centers for Disease Control and Prevention, 1996). Cohen and Shoenfeld (1996) also stated that the relation between vaccination and autoimmunity is obscure. They added that there is a need for experimental studies to address this subject (Cohen and Shoenfeld, 1996). There has been a growing concern among dog owners and veterinarians that the high frequency with which dogs are being vaccinated may lead to autoimmune and other immune-mediated disorders (Dodds, 1988; Smith, 1995). The evidence for this is largely anecdotal and based on case reports. A recent study observed a statistically significant temporal relationship between vaccination and subsequent development of immuno-mediated hemolytic anemia (IMHA) in dogs (Doval and Ciger, 1996). Although this does not necessarily indicate a causal relationship, it is the strongest evidence to date for vaccine-induced autoimmune disease in the dog. We are investigating the effect of vaccination on dogs in a series of experimental studies. The goals of these experiments are (1) to determine if vaccination of dogs affects the function of the immune system and, in particular, if vaccination results in autoimmunity; (2) to delineate the mechanisms by which vaccination results in autoimmunity if this occurs; and (3) to develop alternative vaccination strategies that will not be accompanied by adverse effects. The issue that is the focus of this and ongoing studies in our laboratory is somewhat different from that examined by Duval and Ciger (1996). In their study, a statistically significant temporal relationship between the onset of IMHA and prior vaccination suggested that vaccination caused IMHA or accelerated preexisting IMHA in adult dogs. Although not documented, it is likely that these middle-aged dogs had received multiple vaccines prior to the last vaccination. Why this last vaccination suddenly triggered the onset of IMHA is unknown. In contrast, our studies examine if vaccination of dogs at a young age causes alterations in the immune system, including the production of autoantibodies, that could eventually lead to autoimmune disease in susceptible individuals. In this paper, we report on the findings of the first study in which a group of vaccinated dogs and a group of unvaccinated dogs were followed for 14 weeks after the first vaccination. II. Materials and Methods A. Animals Two pregnant Beagle dogs were purchased from a commercial breeder. The animals whelped in the Animal Facility of the Purdue University School of Veterinary Medicine and the pups were weaned at 6 weeks of age. Five pups were assigned to one of two groups, a vaccinated and an unvaccinated group, based on body weight, gender, and litter of origin. The vaccinated and unvaccinated group of dogs were housed in separate rooms. The dogs were examined daily. Rectal temperature and body weight were recorded twice a week. Blood samples were collected from the jugular vein prior to each vaccination and 2, 5, 7, and 14 days following vaccination for hematology, endocrinology, and viral serology. Blood samples collected on days 5 and 14 following vaccination were also used for lymphocyte phenotyping and lymphocyte proliferation assays, and blood samples collect at 7 days following vaccination were used for the detection of autoantibodies. B. Vaccination Schedule The dogs in the vaccinated group were injected subcutaneously with a commercially available multivalent vaccine, Vanguard-5 CV/L (Pfizer, Croton, CT) at 8, 10, 12, 16, and 20 weeks of age according to the instructions of the manufacturer. They were injected subcutaneously with an inactivated rabies vaccine, Imrab-2 (Rhone-Mericux, GA) at 16 weeks of age. The unvaccinated group of dogs received subcutaneous injections of sterile saline at the same time points. Both groups of dogs were injected subcutaneously with 1 mg of keyhole limpet hemocyanin (KLH, Calbiochem) in RIBI-adjuvant at week 20. C. Viral Serology Serum samples collected at 6 weeks of age and 0, 2, 5, 7, and 14 days after each vaccination were assayed for the presence of antibodies to canine distemper virus by serum neutralization test, and for antibodies against canine parvovirus by hemagglutination inhibition test. Serum samples were analyzed for antibodies against rabies virus at 16 and 20 weeks of age by a rapid fluorescent focus inhibition test. D. Hematology Blood samples were collected at 0, 2, 5, 7, and 14 days after each vaccination for hematocrit, corrected white blood cell count and differential, and platelet counts. E. Endocrinology Plasma and serum samples collected at 0, 2, 5, 7, and 14 days after each vaccination were assayed for curtisol, triiodothymonine (T3), and thyroxine (T4) by radioimmunoassay. F. Immunology Lymphocyte phenotyping was used. Whole blood was stained with a panel of mouse monoclonal antibodies, followed by F(ab')2 goat anti-mouse IgG (Jackson Research Laboratories). The monoclonal antibodies used were CA2.1D6 (anti-CD21), CA15.8G7 (anti-TCRoB), CA20.8H1 (anti-TCRv81, 12.125 (anti-CD4), and 1.140 (anti-CD. The characteristics of these monoclonal antibodies have been described (Gebhard and Carter, 1992; Moore et al., 1995). Following red blood cell lysis and fixation in 2% paraformaldehyde, the cells were analyzed by flow cytometry. G. Lymphocyte Blastogenosis Assay Heparinized blood samples were diluted 1:10 in RPM1-1640 and distributed in the wells of a 96-well plate. Triplicate samples were incubated for 96 hours in the presence of medium only, 2.5 and 5 pg/ml PHA, 5 and 10 pg/ml Concenavalin A (Con A) and 1 and 10 pg/ml PWM. During the last 24 hours of incubation the wells were pubed with 0.5 uCi of H-thymidine. The cells were harvested with a 96-well cell harvester, and the incorporation of radioactivity was measured in a TopCount scintillation counter (Packard Instrument Co., Meriden, CT). H. Enzyme-Linked Immunosorbent Assay (ELISA) The presence of antibodies reactive with homologous and heterologous antigens in serum samples collected at 22 weeks of age was analyzed by an indirect ELISA. High-binding ELISA plates (Costar, Cambridge, MA) were coated with 10 pg/ml of antigen in 0.1 M bicarbonate buffer. The wells were rinsed and incubated for 1 hour with phosphate-buffered saline (PBS)/0.1% Tween. Serum samples were diluted 1:10 in PBS and added to the wells in triplicate. Following incubation, the wells were rinsed and incubated with alkaline phosphatase labeled goat anti-dog IgG (Kirkegnard and Perry, Gaithersburg, MD). Alkaline phosphatase activity was measured after addition of p-NPP substrate at 405 nm in a microplate reader (Molecular Devices, Menlo Park, CA). Essentially the same procedure was used to measure the presence of antibodies against KLH. Alkaline phosphatase labeled anti-dog IgM and IgG were used as secondary reagents. I. Necropsy At 22 weeks of age, the dogs were killed by intravenous injection of barbiturates, and a complete necropsy performed. Tissue samples were collected in 10% buffered formalin and processed for light microscopic examination. The tissues that were examined included the spleen, lymph nodes, tonsils, thymus, Psyer's patches, adrenal glands, thyroid glands, pituitary gland, pancreas, heart, lung, kidney, liver, and brain. J. Statistical Analysis Data were analyzed for significant differences between groups by Student's t test or repeated measures ANOVA and a significant change over time using a repeated measures ANOVA. III. Results A. Viral Serology None of the pups had detectable antibodies against canine distemper virus and canine parvovirus at 6 weeks of age and against rabies virus at 16 weeks of age. The unvaccinated dogs remained seronegative for these three viruses during the course of the study. The dogs that were immunized developed titers against CDV (maximum titers ranged from 1:48 to 1:1024), CPV-2 (1:320 to 1:1280), and rabies (1:25 to 1:1000). B. Clinical Observations, Hematology, and Endocrinology No differences between the unvaccinated and vaccinated groups were found for rectal temperature, body weight, and hematologic values. There were no significant differences between unvaccinated and vaccinated dogs for concentrations of cortisol, T3, and T4. However, a significant (p<0.02) change was observed over time for each of these three hormones. The plasma concentration of cortisol decreased from a mean of 41.1 ng/ml at 8 weeks of age to 17.6 ng/ml at 22 weeks of age. The concentration of T4 also decreased, from 31.1 ng/ml at 8 weeks of age to 22.8 ng/ml at 22 weeks of age. The concentration of T3 increased from 0.63 ng/ml at 8 weeks of age to 1.1 ng/ml at 22 weeks of age. C. Immunology No differences were observed unvaccinated and vaccinated dogs for lymphocyte subpopulations or for the proliferative response to any of the mitogens tested. The response of both groups of dogs to KLH was similar. There was no statistically significant difference in the KLH-specific IgM and IgG concentrations in the serum (not shown). At 8 weeks of age, antibodies against homologous and conserved heterologous antigens were negligible in the serum of the dogs. At 22 weeks of age there was a significant increase of IgG antibodies reactive with 10 of 17 antigens in the vaccinated dogs versus no increase in the unvaccinated dogs (Table I). The increase of optical density was modest for 8 of these 10 antigens, but a large increase was observed for fibronectin and laminin. All vaccinated dogs developed high levels of fibronectin-specific IgG antibodies. Similar levels of IgG anti-fibronectin antibodies were observed when bovine fibronectin was substituted by human or mouse fibronectin (not shown). The concentration of anti-fibronectin antibodies began to increase after the second vaccination in three dogs and after the third vaccination in the other two vaccinated dogs, and reached a maximum level after the fourth vaccination (Fig. 1). To determine if the antibodies had a preferential reactivity with a particular part of the bironectin molecule, we tested the reactivity of serum samples with two fragments of the fibronectin. The 30-kDa fragments contains the heparin-binding domain of fibronectin, whereas the 45-kDa fragment contains the collagen-binding domain. As shown in Fig. 2, little reactivity was observed with the 45-kDa fragment, but significant reactivity was observed with the 30-kDa fragment. High levels of anti-laminin antibodies were observed in the serum of three of the five vaccinated dogs at 22 weeks of age. One dog had high levels at 17 weeks of age, whereas the other two dogs did not devlop high levels until the end of the study. High levels of antibodies reactive with skeletal muscle myosin and myoglobin were observed in both groups of dogs at 22 weeks of age. The antibody levels increased at 11 weeks of age in three dogs, at 13 weeks of age in another three dogs, and at 17 weeks of age in the remaining four dogs. D. Necropsy Gross and light microscopic examination of the tissues of the dogs revealed no significant lesions. The thyroid gland of one of the vaccinated dogs had a small lymphoid nodule with obliteration of adjacent thyroid follicles. IV. Discussion In this study, we exhaustively evaluated the effects of vaccination with a multivalent vaccine and a rabies vaccine on the immune system of young dogs. Vaccination did not cause immunosuppression or alter the response to an unrelated antigen (KLH). In contrast to an earlier study (Mastro et al., 1986), but in agreement with other work (Phillips and Schultz, 1987), we did not observe a transient lymphopenia in the dogs at any time. However, vaccination did induce autoantibodies and antibodies to conserved heterologous antigens. The pathogenic significance of these autoantibodies is presently uncertain. We did not find any evidence of autoimmune disease in the vaccinated dogs, but the study was terminated when the dogs were 22 weeks of age, well before autoimmune diseases usually become clinically apparent. It is likely that genetic and environmental factors will trigger the onset of clinical autoimmune disease in a small percentage of the animals that develop autoantibodies. For practical and economic reasons, only a small number of dogs can be followed in an experimental study, and clinical autoimmune disease may, therefore, never be observed. The principal value of an experimental study is that it enables us to determine the frequency of autoantibody responses and the mechanism(s) that cause vaccines to induce autoantibodies. We used two vaccines, a multivalent vaccine and an inactivated rabies vaccine of a particular commonly used brand. We consider it unlikely that the observed autoantibodies were specifically induced in response to those brands of vaccine and this phenomenon will likely occur with other commercial vaccines. In a follow-up study, we have observed similar autoimmune phenomena in dogs immunized with the multivalent vaccine only and in dogs immunized with the rabies vaccine only (unpublished observations).There was a marked increase of autoantibodies to the skeletal muscle proteins, myoglobin and myosin, in both groups of dogs. The reason for the appearance of these antibodies is uncertain, but it may be the result of the frequent blood sampling of the dogs. The dogs were bled five times following each vaccination, and some tissue trauma was unavoidable.We examined the thyroid and adrenal cortical function in the dogs, and did not find evidence of any abnormality. Autoimmune thyroiditis is one of the most common autoimmune diseases of dogs, and it has been suggested that the apparent increase of this condition in dogs is related to the increased frequency of vaccination with modified live vaccines. There was no increase of anti-thyroglobulin antibodies in the vaccinated animals, or other evidence of thyroid dysfunction. However, the lymphoid nodule found in the thyroid gland of one of the vaccinated dogs may be an early manifestation of thyroiditis, a common lesion in purpose bred Beagles (Fritz et al., 1970).The most strikingly increased concentrations of autoantibodies were directed against fibronectin and laminin. Fibronectin is widely distributed in the body as a component of the extracellular matrix and plasma. The anti-fibronectin antibodies were reactive with fibronectin of bovine, murine, and human origin. Although we have not yet demonstrated that they also react with canine fibronectin, this is very likely, since fibronectin is highly conserved between species. Anti-fibronectin antibodies have been found in human patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis, and a patient with a poorly defined connective tissue disease (Henane et al., 1986; Atta et al., 1994, 1995; Girard et al., 1995). The anti-fibronectin antibodies in four human SLE patients were directed against the collagen-binding domain (Atta et al., 1994), in contrast to the anti-fibronectin antibodies in the vaccinated dogs, which showed no affinity for this domain. The anti-fibronectin antibodies in the human patient with connective tissue disease showed reactivity with the cell-binding domain of fibronectin (Girard et al., 1995).Anti-fibronectin antibodies have been experimentally induced in rabbits by immunization with human fibronectin in complete Freund's adjuvant (Murphy-Ullrich et al., 1984). The antibodies were reactive with both human and rabbit fibronectin. The rabbits subsequently developed a glomernlopathy with granular deposits suggestive of immune complexes in the glomcrular basement membrane. Anti-fibronectin antibodies have been induced in mice by multiple injections of homologous fibronectin without adjuvant (Murphy-Ulrich et al., 1986). The titer of anti-fibronectin antibodies was much lower in mice immunized with native fibronectin than in mice immunized with de-natured fibronectin. However, in both groups, immune complexes were present in the serum and in the glomerali (Murphy-Ullrich et al., 1986). Light microscopic examination of the glomerali of the kidneys of vaccinated dogs did not reveal evidence of glomerunfpathy, but we cannot exclude the possibility of sub-light microscopic lesions.Anti-laminin antibodies were prevalent in the serum of three of the five vaccinated dogs. Anti-laminin antibodies are increased in human patients with SLE, rheumatoid arthritis, and vasculitis. Injection of polyclonal anti-laminin antibodies into rats resulted in glocnerulopathay and proteinuria (Abrahamson and Caulfield, 1982)> Anti-laminin antibodies have also been implicated in glomaerular disease in rats induced by mercuric chloride (Aten et al., 1995).The mechanisms that may underlie the production of autoantibodies following vaccination are unknown, but at least four mechanisms can be proposed: cross-reactivity with vaccine-components, somatic mutation of immunoglobulin variable genes, "bystander activation" of self-reactive lymphocytes, and polyclonal activation of lymphocytes. Perhaps the simplest and most likely mechanism is that of cross-reactivity of vaccine and self-antigens. (Schattner and Rager-Ziaman, 1990), the most likely sources of cross-reactive epitopes are bovine serum and cell culture components. These are present in almost all vaccines as residual components of the cell culture necessary to generate vaccine viruses and may purposely be added to the vaccine as a stabilizer. In the presence of an adjuvant, these bovine products stimulate a strong immune response and induce antibodies that cross-react with conserved canine antigens. Thus, the strong response to fibronectin in the vaccinated dogs is most likely the result of the injection of bovine fibronectin contaminants in the vaccine. Indeed, this is essentially identical to the protocol used to produce anti-fibronectin antibodies in rabbits with human fibronectin in complete Freund's adjuvant (Murphy-Ullrich et al., 1984), as mentioned above. The lower response to other antigens (e.g., cardiolipin and laminin) may be due to a lower concentration of these antigens in the vaccine or lower immunogenicity.During every immune response, self-reactive B and T lymphocytes are generated and activated. This is the result of somatic mutation and bystander activation. Under normal conditions, this will not lead to significant production of autoantibodies, because of the selection process in the germinal centers of lymph nodes. In the germinal centers only B cells that successfully compete for interaction with antigen presented on the surface of follicular dendritic celia will be allowed to survive (MacLennan, 1994). These B cells generally have high-affinity receptors for the antigen to which the immune response was induced. B cells with low affinity for the antigen or affinity for other antigens, including self-antigens, will undergo programmed cell death. The B cells with high-affinity receptors express bc1-2, which may rescue them from programmed cell death (MacLennan, 1994). This mechanism was elegantly demonstrated in mice immunized with a nominal antigen phosphorylcholine (Ray et al., 1996). A single point mutation in the hypervariable region of the expressed immunoglobulin genes was sufficient for the phosphorylcholine-specific B cells to acquire specificity for DNA. However, it was only possible to demonstrate DNA-specific B cells by fusing germinal center B cells with celia that expressed high levels of bc1-2, thereby rescuing them from programmed cell death (Ray et al., 1996). An increased expression of bc1-2 was observed in thymic lymphoid follicles of patients with myasthenia gravis, suggesting that failure to delete self-reactive B cells in these patients may lead to autoimmune disease (Shiono et al., 1997). While this may seem an attractive hypothesis to explain autoimmune phenomena in human beings and dogs, there is currently no evidence that this is a common mechanism.Finally, polyclonal activation of lymphocytes, including activation of self-reactive lymphocytes, is a possible mechanism of vaccine-induced autoimmunity. Certain viruses and bacteria have superantigen or mitegen activity (Schwarts, 1993). This could also be the case for the microbial products included in the vaccines. The present study does not support this mechanism. Firstly, antibodies were observed against 10 of 17 antigens tested. Secondly, the anti-fibronectin antibodies did not react with any portion of the fibronectin molecule, but instead, reacted most strongly with the heparin binding domain. These observations indicate that the appearance of autoantibodies in the serum of vaccinated dogs is an antigen-driven process and not caused by polyclonal activation. As argued earlier, the main antigens implicated are cell culture contaminants and bovine serum components.In the dog, certain autoimmune diseases occur more frequently in particular breeds of dogs, indicating genetically determined susceptibility (Dodds, 1983; Happ, 1995). There is abundant evidence from studies in rodents and human beings that the magnitude of the antibody response and the susceptibility to autoimmune disease are in part genetically determined (Schwartz, 1993). It is likely that genetic factors also determine the susceptibility to vaccine-induced autoimmunity. That this is indeed the case is suggested by the finding that only three of the five vaccinated dogs developed a strong anti-laminin antibody response and that the kinetics of the anti-fibronectin response differed between individual animals. Identification of susceptibility genes will be important, because it may shed light on the pathogenesis of the autoimmunity. In addition, it will provide genetic tests that will enable dog breeders to monitor the susceptibility of their breeding stock to vaccine-induced autoimmunity.Although the pathogenic significance of the vaccine-induced autoantibodies is still unclear, there are a number of ways to prevent their induction. Not vaccinating dogs is not a viable option, because the benefits of vaccination clearly outweigh the still uncertain risks of immune-mediated disease. However, since bovine serum components in the vaccine may be responsible for the majority of autoantibodies, elimination of these bovine components may avoid this problem. This could be accomplished by substituting homologous serum for bovine serum. However, as mentioned earlier, anti-fibronectin antibodies may still be induced by immunization with homologous fibronectin. New generations of vaccines, especially naked DNA vaccines, are free of serum components, and these should not induce autoantibodies. A recent study in mice indicates that DNA vaccination does not induce or accelerate autoimmune disease (Mer et al., 1997). Finally, mucosal vaccines are less likely to induce autoantibodies than parenterally administered vaccines. Depending on the formulation of the vaccine, soluble serum components are less likely to be absorbed via the mocosal surface, and, in fact, may induce tolerance instead of autoantibodies (Weiner et al., 1994).In conclusion, we have demonstrated that vaccination of dogs using a routine protocol and commonly used vaccines, induces autoantibodies. The autoantibody response appears to be antigen driven, probably directed against bovine antigens that contaminate vaccines as a result of the cell culture process and/or as stabilizers. The pathogenic significance of these autoantibodies has not yet been determined.AcknowledgmentsThe authors thank Cheryl Anderson and Julie Tobelski-Crippen for animal care and technical support, and Nita Glickman for data management. This work is supported by the John and Winifred Hayward Foundation.

Christine.

Hang on let me put another ink cartridge and paper in my printer

This should make very interesting reading.

Finally Schultz, another expert

In: Recent Advances in Canine Infectious Diseases, Carmichael L. (Ed.)
International Veterinary Information Service, Ithaca NY (www.ivis.org), 2000; A0110.0500

Considerations in Designing Effective and Safe Vaccination Programs for Dogs (Last Updated: 5-May-2000 )
R. D. Schultz



Introduction
During the past 50 years many vaccines have been developed to prevent a variety of infectious diseases of dogs. Currently there are 16 canine vaccines licensed in the USA which are available commercially (Table 1). Although a few of the vaccines are available as monovalent products (e.g. rabies, canine parvovirus), most are available only as multi-component products that contain between 2 to 10 components. Some vaccines have had a profound effect by reducing, or eliminating, diseases characterized by moderate to high morbidity and/or mortality. However, other vaccines have had little or no recognized beneficial effect because they were designed to prevent infections that cause little or no morbidity and/or mortality. Some vaccines are so new that the potential benefits they provide are not known e.g., Giardia, Leptospira (L.) grippotyphosa and L. pomona.

Table 1. List of the Licensed Canine Vaccines Available Commercially in the United States 1.
Viral Bacterial Parasite

Canine Distemper Virus (MLV)
Canarypox-Distemper Virus (LRV)
Canine Distemper Virus/Measles Virus (MLV)
Canine Parvovirus-2 (MLV, K)
Canine Adenovirus-1 (K)
Canine Adenovirus-2 (MLV, K)
Canine Parainfluenza Virus (MLV)
Canine Coronavirus (MLV, K)
Rabies Virus (K)


Bordetella bronchiseptica (MLV, K)
Borrelia burgdorferi (Lyme) (K, KR)
Leptospira canicola (K)
Leptospira grippotyphosa (K)
Leptospira icterohaemorrhagiae (K)
Leptospira pomona (K)

Giardia (K)


MLV = Modified Live Vaccine; KR = Killed Recombinant Vaccine; K = Killed Vaccine; LRV = Live Recombinant Vaccine
1 Only a few of these vaccines are available as monovalent products. Almost all commercial products contain two or more of these vaccines. The most common multi-component product contain CDV, CPV-2, CAV-2, CPI, Leptospira canicola, Leptospira icterohaemorrhagiae. This product is often referred to as a "7-way vaccine" because it should protect against (CAV-2 and CAV-1) in addition to the other 5 components.

"Core" Vaccines
Canine vaccines which are considered essential, and should be given to every dog, are termed "core vaccines". All other vaccines are regarded as "non-core" and should be used in dogs considered at high risk on an as needed basis. Core vaccines are considered essential because they are designed to prevent important diseases that pose serious health threats to susceptible dogs, irrespective of geographic location or the life style of a dog. Some "non-core" vaccines also may be considered "core" because they are designed to prevent a disease that is a potential public health threat.
Efficacy and safety of a product are critical in deciding whether a vaccine should be considered core. Diseases that pose a serious risk to susceptible dogs, or to public health, which are readily preventable by current vaccines include rabies, a major public health disease caused by the rabies virus (RV); canine parvovirosis caused by canine parvovirus-2 (CPV-2); canine distemper caused by canine distemper virus (CDV), and infectious canine hepatitis (ICH) caused by canine adenovirus type-1 (CAV-1). ICH is effectively controlled by canine adenovirus-2 (CAV-2) vaccine which has replaced CAV-1 vaccines because it is much safer. As part of a minimum disease prevention program, every dog should receive CPV-2, CDV, CAV-2 and rabies vaccines at least one time at or after the age of 12 weeks (Table 2). If that were the only vaccination a dog ever received, and the products used were modified live CPV-2, CDV, CAV-2 and a 3-year killed rabies, the dog would have a >80% probability of developing immunity to those four viruses for 3 or more years.
Vaccination programs for highly contagious diseases are most effective when all, or the highest percentage possible, of animals in the population have been vaccinated. Therefore, every effort should be made to ensure that as many dogs as possible over the age of 12 weeks are vaccinated with at least one dose of the four core vaccines.

Table 2. Duration of Immunity and Efficacy for Canine Vaccines Commercially Available in the United States.
Vaccine Minimum Duration of Immunity Estimate of Relative Efficacy (%)
Core
Canine Distemper >7 yr1 >90
Canine Parvovirus-2 >7 yr1 >90
Canine Adenovirus-2 >7 yr1 >90
Rabies Virus >3 yr1 >85
Non-Core
Canine Coronavirus "lifetime"3,5 ---
Canine Parainfluenza >3 yr1 >80
Bordetella bronchiseptica <1 yr1,2 < 70
Leptospira canicola <1 yr2 < 50
Leptospira grippotyphosa <1 yr4 ---
Leptospira icterohaemorrhagiae <1 yr2 < 75
Leptospira pomona <1 yr4 ---
Borrelia burgdorferi (Lyme disease) >1 yr1 < 75
Giardia <1 yr4 ---


1 Experimental challenge studies and/or serologic studies have been performed. Field experience during outbreaks also confirm experimental challenge studies.
2 Based on field experience and observations from outbreak studies and clinical records. Reliable experimental or controlled studies often not available.
3 Not available; cannot be determined. CCV has not been shown to cause significant disease.
4 Vaccines recently licenced; information not available except from company data.
5 See text.

Minimum Disease Prevention
In the United States, which has the highest percentage of vaccinated dogs, I estimate that less than 60% of all dogs receive the minimum disease prevention vaccination program (Table 3). In many countries less than 30% of dogs receive this one time vaccination with the four core vaccines. Efforts to increase the percentage of vaccinated dogs will require a better understanding by veterinarians and dog owners of the importance, effectiveness and safety of this one time vaccination program. In contrast to a minimum disease prevention program, the vaccination programs for the majority of well cared for pets are vaccination practices considered to provide "maximum disease prevention". Thus, most pet dogs receiving routine veterinary care are given the core vaccines several times; in addition, they routinely receive several of the non-core vaccines. Based on a national survey that we have done during the past 2 years, a majority of veterinary practices began the puppy vaccination program at, or shortly after, 6 weeks of age. The product used most often was a multi-component vaccine containing CPV-2, CDV, CAV, canine parainfluenza (CPI) virus, and L. canicola plus L. icterohemorrhagiae bacterins. Approximately 50% of dogs received Canine Coronavirus (CCV) in combination or as a separate vaccine. The pups were then revaccinated 3 to 5 times with the same product at 2 to 4 week intervals until they reach an age of 14 to 18 weeks. One dose of rabies vaccine was given at 12 to 16 weeks of age. In approximately 25% of animals, two or more doses of an intranasal vaccine containing Bordetella bronchiseptica (B. bronchiseptica) and CPI-virus was given to pups before 18 weeks of age! Additionally, Lyme vaccine (Borrelia burgdorferi) is sometimes included in the puppy program. In the majority of practices, dogs would then be revaccinated with the vaccines noted above at least annually for the remainder of their lives. An exception to annual revaccination is rabies, which would be given at 1 year of age, and then once every 3 years thereafter, unless more frequent vaccination was required by law or believed necessary by the veterinarian.



Table 3. Vaccination Programs for Dogs.

"Core" Vaccines (Every Dog)
Program A - Minimal Approach
Primary Immunization at 12 weeks or older
- Canine parvovirus-2 (CPV-2)
- Canine Distemper Virus (CDV)
- Canine Adenovirus (CAV-2) and Rabies Virus
Note: Canine Parainfluenza (CPI) will have to be included since there are no products with CPV-2, CDV and CAV-2 without CPI.
Revaccination
Rabies - 1 year after primary, then once every 3 years.
Other vaccines would not be given again.
Program B - Moderate Approach Primary Immunization
- 6 to 9 weeks - CPV-2 + CDV
- 12 to 15 weeks - Rabies, CPV-2 + CDV + CAV-2 + CPI*
Revaccination
- 1 Yr. later - Rabies, CPV-2 + CDV + CAV-2 + CPI*, then again every 3 years for rabies; every 3 -5 years for other vaccines.
*See note under Program A
Program C - Maximal Approach
Primary Immunization
- 6 to 8 weeks - CPV-2 +CDV - 9 to 11 weeks - CPV-2 + CDV + CAV-2 + CPI* - 12 to 14 weeks - Rabies, CPV-2 + CDV + CAV-2 +CPI*
Revaccination
- 1 Yr CPV-2 + CDV + CAV-2 + CPI* + Rabies. - 3 Yr CPV-2 + CDV + CAV-2 + CPI* + Rabies. *See note under Program A
"Non-Core" Vaccines
(Give only if the dog is at high risk and then only the vaccine that is needed)
Program D - Minimal Approach
- Give only "core" vaccines ("Non-core" vaccines are not given)
Program E - Moderate Approach
Primary Immunization
- 6 weeks of age, or older - 1 dose of intranasal B. bronchiseptica + CPI*
- 12 week and 14 to 15 weeks - 2 doses of Leptospira bacterin (2- or 4-serovars)
Revaccination
- Annually - Leptospira bacterin + intranasal B. bronchiseptica + CPI*
*See note under Program A
Program F - Maximal Approach
Primary Immunization - 6 to 14 weeks of age - 2 doses Intranasal B. bronchiseptica + CPI*
- 9 to 11 weeks and 12 to 14 weeks - Leptospira bacterin (2-serovars or 4-serovars)
- 9 to 11 and 12 to 14 weeks - 2 doses Lyme disease vaccine
- 6 to 8 weeks and 9 to 11 weeks - 2 doses Giardia vaccine
*See note under Program A
Revaccination
- Annually with intranasal B. bronchiseptica and CPI
- At least annually with Leptospira bacterin (2-serovars or 4-serovars)
- Lyme vaccine - annually, a few months prior to peak tick season
- Omit Giardia vaccine
Additional Recomendations
When Canine Parvovirus is a serious threat:
- CPV-2 monovalent MLV product starting at 5 weeks of age then giving the product every other week until 15 weeks of age. A more reliable program would be to determine antibody titers to CPV-2 and vaccinate pups when CPV-2 antibodies no longer interfere with immunization.
When Canine Distemper is a serious threat:
- Measles virus - CDV combination at 4 to 6 weeks of age; then a product containing CDV without MV at 12 weeks of age or older.
Program A, B, or C for "core" products can be matched with any of the "non-core" product programs D, E, or F. Therefore, Program A can be matched with D (no "non-core" product given) or with F, where any of the non-core vaccines needed could be given and given again annually for dogs at high risk. Vaccination more often than listed in C and F should rarely, if ever, be done.

Considering the difference between the minimum disease prevention program that protects >80% of dogs from the important canine diseases and the program described above, it is not surprising that neither the dog-owning public nor veterinarians appreciate the exceptional benefit derived from the "minimum disease prevention program".
Why are there significant differences in number of doses and components of vaccines routinely given in the maximum vs. minimum disease prevention programs? Those differences arise primarily from misperceptions about how vaccines work, which vaccines are necessary, and how often vaccines should be given during the life of the dog to provide protective immunity.

Common Questions Regarding Vaccines/Vaccination


At what age should the vaccination program begin?
How often does a dog need to be revaccinated? (What is the duration of immunity?)
How does one determine the risk of disease, and therefore the necessity for one or more of the "non-core" vaccines?
How effective are the vaccines?
Do all current vaccines for a given disease provide similar protection?
What are the risks of causing adverse reactions with certain vaccines or when giving vaccines too often?

Those questions are being asked more now than in the past since most vaccine experts, and many dog owners, believe that certain vaccines are given too often and some are unnecessary. Answers to the above questions are complex and depend on the needs of a particular animal as well as the expectations of the owner and veterinarian. [1-5].

At What Age and Which Vaccines to Use?
Unfortunately, simple and universally agreed on answers are not available. Most experts agree that puppy vaccination programs should begin at 6 to 9 weeks of age; the first puppy vaccination should begin prior to 6 weeks of age only in special situations, e.g., humane shelters. Vaccination at less than 6 weeks of age is often not effective due to interference of vaccinal immunity by passively acquired antibodies and, rarely (e.g. <2 weeks of age), inability of a pup's immune system to respond effectively to the vaccine. Ideally, pups should be kept in a clean environment prior to vaccination and have no, or minimal, contact with dogs other than the dam and littermates. The first and second doses of vaccine in a puppy series optimally includes only the CPV-2 and CDV components. Those are the most important vaccines for a pup less than 12 weeks of age because canine parvovirus and canine distemper are the two most serious infectious diseases of dogs.
CPV-2 is now the most important vaccine in the USA since pups are most likely to encounter this virus because of its high prevalence and environmental stability. When CDV is a major threat to young pups, as in known distemper-infected kennels or humane shelters, the most effective product is the combined measles virus (MV)-CDV vaccine. This product can be used in pups as young as 4 weeks of age when necessary. When MV-CDV is used, revaccination should be done with a CDV product that does not contain MV. After 9 weeks of age, the vaccine regimen should include a rabies vaccine (12 weeks or older) and multi-component vaccines (CPV-2, CDV and CAV). All current commercial products also contain CPI virus, however, CPI is not needed in the parenteral vaccine since it is often given and is more effective when given intranasally in combination with B. bronchiseptica. Intranasal products are available which contain CAV-2 in addition to B. bronchiseptica and CPI. Use of the three-way intranasal product would eliminate the need to give CPI and CAV-2 parenterally.
Leptospira bacterins, if needed, should ideally be given at 9 weeks of age or older. Leptospira bacterins require two doses of vaccine which should be given at intervals of 2 to 4 weeks between doses. Multiple doses of modified live viral vaccines are generally required only in pups less than 12 weeks of age because after this age passively acquired antibodies from the dam have usually declined below levels which prevent successful immunization. When MLV vaccines are given to pups that have lost their passively acquired antibody (~12 weeks of age), a single dose of vaccine can immunize. Multiple doses are required for primary vaccination with certain killed vaccines (e.g. Leptospira spp., Lyme disease) but single doses are sufficient when revaccinating at a later time, usually at 1 year. Due to improvements in multi-component core vaccines, especially the CPV-2 component, and the lower antibody titers of dogs in vaccinated populations it is no longer necessary to administer vaccines through the age of 18 to 20 weeks. Previous recommendations for the last dose of vaccine at 18 or 20 weeks were made in the 1980's and early '90's because CPV-2 vaccines failed to immunize a high percentage of pups even when passively acquired antibody titers were well below the level of antibody that provided protection from infection with virulent virus. [3,6] Also at that time, a large proportion of dogs had antibodies recently engendered by virulent virus, rather than vaccines. The "window of vulnerability" ("critical period" - see Canine Parvovirus, U. Truyen, In: Recent Advances in Canine Infectious Diseases, L.E. Carmichael (Ed.), IVIS, Ithaca, NY - Doc. No. A0106.0100), was as long as several months when certain of the older CPV-2 vaccines were used! However, with the improved CPV-2 vaccines now available from the major vaccine manufacturers, the "window of vulnerability" has been reduced to 2 weeks, or less. It is, therefore, not necessary to vaccinate pups beyond 12 to 14 weeks of age. The other core vaccine components also will immunize a majority of dogs when the last dose is given at 12 to 14 weeks of age. [6-8].

How Often to Vaccinate?
Repeated vaccinations with multi-component vaccines need not be repeated at intervals more often than every 2 to 4 weeks in a puppy program. Two to three doses of vaccine should be adequate to immunize when vaccination is started at 6 to 9 weeks. The most important aspect of a puppy vaccination program is to make certain that the last dose of vaccine in the series is given when the animal is at least 12 to 14 weeks of age. However, as mentioned above, pups often receive 4 to 6 doses of the same multi-component vaccine during the first 3 - 4 months of life. The higher number of doses may be justified for animals in humane shelters, commercial kennels, or other areas where animals are at high risk. However, pet dogs in a single or multi-dog household are at low risk of exposure to most diseases. Such animals would not need to be revaccinated every 2 weeks and they should never be vaccinated every week, as practiced in the USA by some breeders and veterinarians. Furthermore, if a dog is at high risk of exposure to an important disease like CPV-2, a monovalent CPV-2 vaccine is recommended, not a multi-component product . The risk of adverse reactions has been greater with multi-component vaccines.

Expected Immunization Success
Since passively acquired antibody declines below the level where it can interfere with the current core vaccines by 12 to 14 weeks of age, modified live CPV-2, CDV and CAV vaccines given at this age will immunize a very high percentage of pups (>90%) and the immunity from that single dose of vaccine will last for several years. Our research on duration of immunity for the CPV-2, CDV and CAV vaccines has demonstrated a minimum duration of immunity of 7 years; the maximum duration of immunity may be for the life of most (>80%) vaccinated animals. Many killed rabies vaccines have a minimum duration of immunity of 3 years. However, a small percentage of pups (<5%) fail to develop immunity to one or more of the core components and a much higher percentage of pups (>25%) fail to develop immunity to certain of the non-core vaccines for a variety of reasons. Reasons which have been given include: The presence of passively acquired antibody at time of last vaccination; delay in maturation of the immune system; poor vaccinal immunogenicity; vaccine not given often enough; genetic inability to respond to certain vaccine antigens; immunosuppression; too many components in a multi-component vaccine; or ineffective lots of vaccine. [9, 10].
To ensure that all pups become immune, one dose of rabies vaccine is given at 12 weeks of age or older, followed by a second dose 1 year later, or at 1 year of age. Revaccination is then done at 3 year intervals. Similarly the CPV-2, CDV and CAV vaccine could be given at 1 year and then every 3 to 5 years without concern about loss of immunity. There is no evidence, or reason, to believe that revaccination with the core vaccines more often than recommended above would provide more effective protection from the important diseases since the minimum duration of immunity from the core vaccines is at least 3 years. States in the USA which require annual revaccination for rabies should remove those requirements because annual revaccinations are unnecessary. Vaccinating the same animal less often also would reduce the risk of adverse reactions. In areas where there is a high risk of rabies, programs must be developed to immunize those dogs that have never been vaccinated or have not been vaccinated within the past 3 or more years. Unvaccinated dogs pose the greatest threat for the transmission of rabies virus, not dogs which have been previously vaccinated or, especially, those vaccinated within the past 3 years. In our studies, pups vaccinated annually with modified live CPV-2, CDV and CAV vaccines received no added benefit from annual revaccination throughout a period of 7 years when compared to dogs that were vaccinated as pups then challenged with virulent virus at 7 years of age. Both groups of dogs were protected from challenge infection with CPV-2, CDV and/or CAV. Therefore, for those vaccines that provide immunity for 3 or more years, I believe that annual revaccination is contraindicated - the increased risk of adverse reactions from revaccination provides no benefit. In contrast, use of those products which provide only a short duration of immunity (~1 year) requires annual, or even more frequent, vaccinations - but only with products that contain vaccine components that are needed in a particular region (e.g. Leptospira or Lyme disease bacterins), not with multi-component products containing unnecessary vaccines.

"Non-Core" Vaccines: Which are Needed and When?
Which "non-core" vaccines are really needed? This question is difficult to answer and depends on the animal and its environment.
Leptospira bacterins - The most important "non-core" vaccine is for leptospirosis since this infection can cause mild to severe illness and it is a zoonosis. The question could be asked why Leptospira bacterins are not included as "core" vaccines? The principal reason concerns vaccine efficacy - a high percentage of vaccinated dogs do not develop protective immunity, or they develop immunity for only a short duration of time. Until recently, bacterins contained only two serovars (L. canicola and L. icterohaemorrhagiae) and cross protection between leptospiral serovars does not occur. Furthermore, the Leptospira sp bacterins are among the more reactogenic components in multi-component vaccines. Clinically, immediate and/or chronic immune-mediated reactions have been observed and, experimentally, multiple types of immune mediated hypersensitivities have been induced with leptospiral antigens. Moreover, Leptospira bacterins do not prevent infection or shedding of the organisms in the urine, even when they reduce or eliminate the clinical signs of disease. Thus, the public health threat from organisms being shed in the environment persists. Finally, Leptospira bacterins are not considered "core vaccines" because leptospirosis is rare in many geographic regions of the USA and few or no clinical cases have occurred for many years. Very recently, new vaccines have been licensed in the USA that contain L. grippotyphosa and L. pomona. The new vaccines should provide broader immunity and, hopefully, will prevent disease caused by those serovars. However, the new vaccine containing the four serovars requires evaluation in a large number of dogs before it is known whether it will reduce the incidence of canine leptospirosis in endemic areas and if adverse reactions are worse than those caused by current products which contain only 2 serovars.
According to our recent survey on vaccination programs, approximately 30% of veterinary practices do not vaccinate for leptospirosis. The responding practitioners either didn't believe that leptospirosis was a significant problem in their area or the vaccine containing L. canicola and L. icterohaemorrhagiae serovars failed to provide protection. Also, there were concerns about adverse reactions when the current products were used. Approximately 50% of the veterinarians completing the survey must have felt leptospirosis was a significant problem since they vaccinated >75% of the dogs with the products containing L. canicola+icterohemorrhagiae. According to our survey Leptospira bacterins were used in more dogs than any of the other "non-core" vaccines except CPI.
Canine parainfluenza and B. bronchiseptica - CPI is included as a component of all current parenteral vaccines containing CDV, CPV-2 and CAV; therefore, it is given to every dog that receives the core vaccine. Approximately 80% of practices surveyed vaccinated less than 50% of dogs with B. bronchiseptica. The product used most often for kennel cough was an intranasal vaccine that contained both B. bronchiseptica and CPI. Many non-vaccinated dogs never develop "kennel cough" or they develop mild, self-limiting disease; however, other dogs, both vaccinated and non-vaccinated, developed severe, protracted kennel cough requiring treatment. Efficacy of the present kennel cough vaccines is controversial (see: Canine Respiratory Bordetellosis, D. Keil and B. Fenwick, In: Recent Advances in Canine Infectious Diseases, L.E. Carmichael (Ed.), IVIS, Ithaca, NY - Doc. No. A0104.0100) and duration of immunity, if present, would be less than 1 year. Ventilation and hygiene are important in environments where kennel cough is prevalent. In certain kennels, improvement in ventilation has eliminated or reduced the need for kennel cough vaccines. Also, in some environments vaccination at intervals as frequent as every 3 to 6 months failed to significantly reduce respiratory disease.
Coronavirus vaccines - Although approximately 50% of practices routinely use coronavirus vaccine, most vaccine experts agree that this vaccine is not needed. Some experts consider CCV vaccines useless. Clinical disease rarely occurs with CCV infection and when disease does occur it is usually mild, self-limiting and most commonly seen in pups less than 8 weeks of age - an age which is earlier than vaccine would provide benefit. Based on our observations that the preponderance of clinical cases caused by CCV occur in young pups, any "protection" derived from vaccination of pups or from natural infection would, in the practical sense, last a lifetime. Furthermore, CCV alone has not been shown to experimentally cause significant disease in susceptible dogs. The demonstration that CCV can enhance the severity of disease caused by CPV-2, does not suggest a need for CCV vaccine since dogs vaccinated with CPV-2 vaccine only, are completely protected when co-infected with a combination of CCV and CPV-2. [6] CCV vaccine alone provided no protection for dogs challenged with a combination of CCV and CPV-2.
Lyme Disease Vaccine - This vaccine should be used only in areas where Lyme disease is known to occur, and where it may pose a serious threat to the health of the dog. Even in areas where Lyme disease has been shown to be endemic, and where infection with Borrelia burgdorferi is common, clinical illness is rare. When seen, it is often mild and readily treated with antibiotics. In certain highly endemic areas where infection of the natural vectors (mice and deer) is almost 100%, disease in dogs may be more common, and sometimes severe, but cases are responsive to antibiotic treatment.
After the release of the first human Lyme disease vaccine, a segment of the human population with a particular human leukocyte antigen type, determined by genetics, was found at increased risk to developing chronic arthritis after vaccination with the Lyme vaccine. This finding should signal caution in the over use of canine Lyme vaccine since a similar phenomenon may occur in dogs. Lyme disease vaccine, if used, should be given only to dogs that are truly at very high risk of infection/disease.
Giardia vaccine - This relatively new product may be valuable in a highly specialized market, mainly in larger breeding kennels which whelp and raise many puppies. It is unlikely to provide benefit as a routine vaccine. The effectiveness and safety of the Giardia vaccine in those special situations where it is used remains to be determined. Use of this vaccine would likely play an insignificant role in reducing the public health concerns of human Giardia infection.

Adverse Reactions
The risks of adverse reactions from vaccines are not well studied, nor are the adverse reactions rates well documented. Even where documented, the information is not readily available. The immune mediated hypersensitivities caused by vaccines are well known and occur in every species. [4, 10,11] The most commonly observed hypersensitivity is a type I (immediate) reaction which is most often caused by IgE antibody resulting in a local or generalized anaphylaxis. The most common signs of local reactions are facial edema, hives, itching and rarely sneezing; signs of a systemic reaction include urination, vomiting, diarrhea, which is sometimes bloody, dyspnea and collapse. According to a recent survey we have conducted, the most common vaccination reactions observed in dogs include pain, soreness, stiffness and/or lethargy at variable times after vaccination. Swelling, a persistent lump, irritation, hair loss and/or color change of hair at site of injection were also observed as common reactions. A change of behavior was reported in a small percentage of dogs after vaccination. Post-vaccinal neurologic disease (e.g. encephalitis) was rare. All of the reactions noted above generally occur within minutes, hours or days after vaccination; they were, therefore, likely to have been associated with a vaccination. More recently, it has been shown experimentally that dogs develop an autoimmune response after vaccination, something that was known to occur in other species [11].
Furthermore, a study of dogs in veterinary clinics showed a slight increase in cases of autoimmune hemolytic anemia within 30 days following vaccination with multi-component vaccines [12]. It is very difficult to document a "cause and effect" relationship between vaccination and disorders occurring weeks to months after vaccination, but it would not be unexpected for vaccines to trigger immune-mediated disease (including autoimmune disorders) in a small percentage of animals [4, 5, 11, 12]. Adverse reactions from vaccines should not be used as a reason not to vaccinate; instead, it is sensible not to use vaccines which are unnecessary, or to vaccinate more often than needed. In general, bacterial vaccines are more likely to cause immune-mediated reactions than do viral vaccines. Killed vaccines, especially those which contain adjuvants, are more likely to cause adverse reactions than do modified live vaccines. Because immune mediated reactions are genetically determined, some breeds, especially certain families of dogs, are at much greater risk of developing adverse reactions than the canine population as a whole [4].



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Christine.

Expert you`ll all be word perfect tomorrow................
:smt043 :smt043 :smt044 :smt048

Christine.

Gee thanks Christine lots of light bedtime reading there