,;, FELINE VACCINATION: Why it's not "just a shot."

Alice IvI. Wolf, DVM, Dip ACVWI (Internal Medicine), DipABVP (Feline Practice)

Emeritus/Adjunct Professor: Dept. Sm. An. Vet. Clinical Sciences College of Veterinary Medicine Texas A&M University, College Station, TX Chief Medical Consultant: Veterinary Infbrmation Network@

GENERAL CONCEPTS:

Dramatic changes have occurred in the past 18 years regarding the way veterinarians view vaccines and vaccination practices. _The concepts of core and non-core vaccines, disease risk assessment, extended inter-vaccination intervals, and using products that minimize vaccine- associated inflammation are currently mainstream veterinary medicine. There are now a number of pLrblications that doctiment the long duration of imrnunity provided by most feline viral vaccines. The fotuth revision of the American Association of Feline Practitioners (AAFP) Vaccination Gr-ridelines for cats was publishecl in late 2013.-The World Small Anirnal Veterinaly..Association Gr,ridelines were published in 2010. The European Advisory Board on' Cat Diseases (ABCD) also published guidelines in 2009. These are very thorough documents that are exhaustively referenced and are ar1 or-rtstanding resource for veterinary practitioners as they chan-ee vaccination practlces.

a-

Day N{J, Horzinek lvIC, Schultz RD: WSAVA Guidelines for Vaccinarion. ./ Stn Anint Pract 20 10:5 1(6):1'J2.

Horzinek MC. Thiry E,: Vaccines and'vaccination: tlie principles and the polemics. J Feline fuIed Srrrg. July 2009;11(7):530-7. (ABCD Gr-ridelines for Feline Vaccination)

Scherk MA. Ford RB. Gaskell RNI, et al. 2013 AAFP Feline Vaccination Advisory Panel Report. Jountul oJ Feline luleclicine and Surgen- 2013 15: 785-808.

The role of chronic inflammation inducing tnmorigenesis has long been recognized in cats ancl many other species. While a direct association between post-vaccinal chronic inflammation ancl risk of vaccine-associatecl sarcoma (VAS) has not been definitively established, adjuvants have been associated with injection site reaction, injection site granuloma, and chronic inflamrnation in cats. Adjuvant remains (air"rminup par{icles. etc.) have also been found histoiogicallv itr sarcomas, though this does not necessarily provide a causal link either. hi acldition. orher causes of chlonic inflamrnation such as foreign bodies, microchips, retained surgical sponges. ancl nofi- absorbable sutures have also elicited neoplastic development in cats. Very rarely, other injectable agents such as lufennron, repositol depot steroids, meloxicam, cisplatin. have been reported to callse injection site tumors. These othersr.rbstances caLlse this problem so infreqr-rently that this occLlnence merits a case report in the iiterature.

o2014 The WSAVA Gr-ridelines recommend the use of "non-adjuvanted vaccines whenever possible". Meaning, that when alternatives to adjuvanted products are available, these shor-rld be used. Both MLV and recombinant vaccines do NOT contain adjuvant.

The most recent epidemiologic study of injection site tumors (Srivastav JAVMA 2012) in describing tumors from the hindlimbs (sites of FeLV and RV administration using AAFP gr-ridelines) states: "Results consistently showed that case cats [i.e. having VAS] were significantly less likely to have received recombinant vaccines than inactivated [i.e. adjuvantedl vaccines."

CORE VACCINES FOR CATS:

Core vaccines should be given to every patient regardless of lifestyle. Fot cats, the core vaccines inclr"rde: feline parvovirus (panleukopenia), feline herpesvitl-tsl (feline viral rhinotracheitis), feline respiratory calicivirus and rabies.

FVRCP: Modilied live (MLV) FVRCP vaccines are often recommended becanse they are not adjuvanted and do not carry the same risk of inducing chronic vaccine site inf-lammation as killed adjuvanted vaccines. In addition, a recent study has shown more rapid development of immunity against feline parvovirus in kittens given MLV FVRCP compared to those given killed FVRCP vaccine.

Feline Leukemia: In the lnost recent AAFP guidelines, Feline Leukemia (FeLV) vaccine is also recommended as a CORE vaccine for kittens. The reason for recommending nniversai kitten- hood protection against FeLV is becar-rse cats under a year of age are at greatest risk for acquiring this disease, Nearly l00o/o of kittens infected with FeLV at 6 rveeks of age or less will remain persistently infected tor life. At 6 months of age, the risk of persistent infection drops to abor"rt 307c and this decreases further to 5 - I57o atter 12 months due to the development of natural resistance to this disease rvith age. \Vhen rve ask clients abor:t their kitten's environment, they may tell us that the kitten rvill be kept only indoors. However. the kitten may escape or the client may begin allorving the cat or-rtside. The owner may not retllrn the kitten for FeLV vaccination after the pediatric vaccination series has been completed even thoLlgh the kitten's risk of exposLrre to FeLV has changed. By vaccinating the most slrsceptible individuals (young kittens), r,ve rviil provide the best possible protection during the period of highest susceptibility to the disease. After a year of age, if the cat tmly is kept only indoors without exposllre to FeLV- infected cats, we do not need to continlle FeLV vaccine adrninistration. If vaccination is continlled, I recommend that a non'adjuvanted FeLV vaccine that reduces the potential risks associated with adjuvants be used. RABIES: Rabies vaccination is essential for all cats in the US. There were25J confirmed cases of rabies in cats in the U.S. in 2012, the most recent year for which complete data is available. That compares to only 84 cases of rabies diagnosed in dogs during the same period. Cats are more likely to interact non-fatally with potentially rabid wildlife species such as raccoons and skunks. Being an "all indoor cat" is no protection. Bats can inhabit houses and had the second highest incidence of rabies diagnosed in wildlife species with 1680 rabid bats diagnosed tn2012. Bats also are the primary species causing rabies exposlrre in humans each year.

There are multiple choices for rabies vaccination of cats. There are killed, adjuvanted 3-year licensed vaccines and a recombinant, non-adjuvanted, one year Iicensed vaccine (PUREVAX@ Rabies - Merial). One theory is that chronic inflammation is involved in the induction of VAS. Experimental histologic studies of vaccination sites show that non-adjuvanted vaccines produce little to no inflammation, whereas adjuvanted vaccines caLlse inflammatory changes at the site that may persist for long periods of time (Day 2007). In my opinion, it is much better to Llse a non-adjuvanted vaccine lnore frequently rather than any adjuvanted vaccine, regardless of the freqr-rency of use. An additionai advantage of using a rabies vaccine with a one year license is that we can use this to prompt the owner to retnrn for the most impoftant part of the yearly visit, the physical examination and wellness assessment. There are exceptions to every rule. For TNR programs with feral cats that may only be handled at the initial time of trapping and ner"rtering or for "barn cats" that receive little to no veterinary attention and lvili be seen less often than every year, a 3-year licensed vaccine shor.rld be r-rsed because rabies is a pr"rblic health problem.

NON.CORE VACCINES FOR CATS:

FeLV: The FeLV vaccine is considered non-core for adr,rlt cats and each patient shor-rld have an appropriate lifest,vle risk assessment to determine rvhether this vaccine should be used. For cats still at risk that receive revaccination for FeLV, the revaccination schedule should reflect the lif'estyle of the cat.

Intranasal FVRC or FVRCP: This vaccine has particr-rlar use in shelters. catteries, and other sitr-iations r,vhere early and rapid onset of protection is desirable and r.vhere exposLlre to high levels of the URI vimses is expected. Whiie intranasal vaccine with herpesvinis and respiratory calicivirus may be advantageous because this is the natural route of exposlre for these agents, this is not the case for feline parvovirus (panler,rkopenia). The parenteral route is still prefened for this antigen. Intranasai URI vaccines should not be used in retrovirus positive cats because they may be immr.rnosuppressed and develop vaccine-related clinical signs of clisease.

Chlamydophila and, Bordetella are on the AAFP non-core list but I do not recommend giving either of these vaccines to househoid pet cats. Both of these diseases are very Lincommon causes of lrpper respiratory disease and these vaccines are reactive and have a sholt duration of immunity. Chlamydophila or Bordetella bacterins may be helpful for short-term Llse in shelter or cattery situations where an outbreak of upper respiratory disease has occurred if these agents are cr,rltured from a number of cats and confirmed as a major component of the respiratory syndrome.

NOT RECOVIMBNDBD VACCINES FOR CATS:

The feline infectious peritonitis (FIP coronavirus) vaccine is on the WSAVA not recommended list.

Neither the WSAVA nor I recommend the currently available FIV vaccine for a variety of reasons. Not only is the vaccine adjuvanted, but FlV-vaccinated cat will test falsely positive on antibody-based tests (ELISA, Western Blot, IFA) for at least a year post-vaccination. FIV PCR testing is available bllt most tests are not sufficiently accurate to help us differentiate vaccinated from naturally-infected cats. A discriminant ELISA FIV test may have the potential to differentiate vaccinated from infected cats but this test is not commercially available at this tirne.

Virulent Systemic Calicivirus (VS-Calicivirus) is NOT recommended by AAFP. VS-FCV is a rare mlltation of calicivirus that occurs in a crorvded, poorly managed population of cats already carrying caliciviruses. Molecuiar analysis has demonstrated that each VS-FCV isolate is genetically unique and that there is no common mutation that accounts for vimlence. Isolated cases of VS-FCV occur almost exclusively in popr"rlations of cats in group-housed settings r.vith iess than ideal husbandry (sheiters, catteries, resclles, etc.). VS-FCV is not a disease of hoursehold pets and has not spread to the general cat population anywhere. Typically, one to a few cats are affected in these environments and the disease burns itself out and disappears. VS- FCV has not established itself in the hor"rsehold cat popr-rlation anywhere.

Prevention of VS-FCV spread in veterinary hospitals involves avoiding hospitalization of affected cats and treatment of these cats as olltpatients whenever possible. If hospitalization is required, appropriate infectior.rs disease mana-qement rvith strict isolation procedr.rres rvill prevent spread to other cats in the hospital population.

PEDIATRIC VACCINATION:

The goal of pediatric vacciuation is to stirnr-rlate active and solid irnmr-rnity before the sr-rsceptible kitten or pllppy is exposed to pathogenic organisms. This means that we mLlst start a vaccination program early enough to prevent active disease as maiernal antibody wanes.

The pediatric core FVRCP vaccine series shor-rld be started when the kitten is seen for its first pediatric examination at 6-8 weeks of age. Core vaccines should be repeated at 3-4 week intervals until the kitten is 16 weeks of age. Although some biologics manr-rfactrlrers have experimental studies that demonstrate good protection by 12 weeks of age, recent research using conventional kittens indicates that maternal antibody interference with vaccination may persist in some kittens beyond 14 weeks of age. Therefore, the vaccination guidelines recommend administering the final pediatric vaccination at 16 weeks of age or older. Rabies vaccine shor,rld be given at 12 weeks of age or older as per the Rabies Compendium and state/local ordinances. I recommend using only a non-adjuvanted rabies vaccine for cats and a 3-year licensed rabies vaccine tor dogs.

Kittens should be tested negative for FeLV prior to vaccination. In addition to the other serious conseqllences of infection, there is no demonstrated benefit of giving an FeLV vaccine to an FelV-infected cat. I recommend using only non-adjuvanted FeLV vaccine according to the manufacturer' s instructions.

RE.VACCINATION INTERVALS :

FVRCP, FeLV (if given), and RV should be repeated at one year of age. As per AAFP, WSAVA, and ABCD recornmendations, FVRCP is recommended no more frequently than every 3 years after that time. RV should be re-administered according to the manufacturer's licensing approval (l year or 3 years) and according to national/state/local ordinance. FeLV vaccination may be continr-red according to manufacturer's instructions if the cat is at risk of exposllre after I year of age.

VACCINE SAFETY: ADVERSE EVENTS AND HOW TO AVOID TIIEN,I

INTRODUCTION

Adverse events associated with vaccine administration to srnall animals are relativelv rare given the frequency u'ith which vaccir.ies are given to patients and the cornplexity of these biological agents, Tu'o recentiy published str-rdies revierved patient records from the database of a large colporate veterinary clinic netr,vork. The incidence of adverse events associated with vaccination was reported to be approximately 1:200 for cats rvithin 30 days of vaccination. In these studies, yolli.lg animals and cats receiving multiple vaccines/antigens per visit were at higher risk for an adverse event. Unfortunately, the true incidence of adverse events associated with vaccination is stiil largely unknorvn because adverse events may not be recognized as vaccine-related. may not be reported by owners to veterinarians. may not be reported by veterinarians to manufacturers, and because we have no r,rnbiased national database for adverse event reporting to which veterinarians or researchers have access.

DIRECT EFFECTS OF VACCINES

Activation of the immune system by vaccination

Stimr-rlation of the imrnune system by parenteral vaccination may callse malaise. fever, inappetence, and lymphadenopathy due to the activation of immnnologic and inflammatory pathways with resultant increases in lymphokines, interferons, leukotrienes, and other inflammatory mediators. Such reactivity usually appears within 24-48 hours of vaccination and is generally mild, transient, and self-limited. This is the most common post-vaccinal adverse event in cats. The effects of such immune stimr-rlation may be blunted pre- and post-treatment with non-steroidal anti-inflammatory drugs. In animals with a history of a minor adverse event (malaise, fever, lethargy), administering no more than one vaccine per visit and separating individual vaccine administration by 3-4 weeks may aiso help to reduce this adverse event.

Immunosuppression caused by vaccines

Transient immunosuppression associated with vaccination can be demonstrated with modified live virus (MLV) antigens. Rarely, post-vaccinal immunosuppression may allow subclinical opporlunistic infections to become clinically apparent. Often there is no way to predict these events and no way to effectively prevent the potential consequences of immunosuppression. MLV vaccine administration should be avoided in animais receiving cyclosporine and other potent immunosuppressive drugs, and those with known immunodeficiency syndromes.

Local site reactions

Local site reactions include an immediate pain response on injection. transient swelling and pain at the injection site. and intlarnmatory nodr-rles that may persist for weeks to months following vaccination. In the review study of adverse events in cats, the most common adverse event at 30 days post-vaccination was a palpable nodule remaining at the injection site. Avoiding vaccines that contain inflammatory ingredients such as vaccine adjuvant may decrease the incidence of local site reactions.

HYPERSENSITIVITY REACTIONS

Type I Hypersensitivity

Type I hypersensitivity reactions are mediated by IgE and encompass a wide range of acute clinical presentations. These reactions range from minor urticaria./angioedema to dramatic and potentially fatal anaphyiaxis. Cats rarei,v develop Lrnicaria br-rt anaphylaxis is fairly common. The lung is the prirnary shock organ in cats. Cats may also exhibit collapse. cyanosis, vorniting, or diarrhea associated rvith an anaphylactic reactiorr.

We tend to think nanowly about the constituents in our vaccine products. In addition to the desirable antigen(s), there are a number of residual protetns and other potential sensitizing cotnpounds that may remain from the vaccine manufacturing process or that rnay be added as part of that process. Tirese sensitizers may be present in minr:te alnounts br-rt this may be sufficient to stimLllate and then tri_qger the hypersensitivity response tipon subsequent vaccine exposllre. Sensitizers include bovine serum albumin and fibronectin from fetal caif serum used in vilal culttre media, antibiotics r-rsed during viral culture to prevent bacterial overgrowth, ancl casein, gelatin, and other stabilizers used to extend vaccine shelf life. Rarely, type I reactions may occllr with the first vaccine administration. It is believed that matemal transfer of antigen- specific IgE that binds to mast cells in the offspring accollnts for these unusual and unexpected reactions.

If the offending sensitizer can be recognized, ideally it should be avoided. A recent report suggests that intradermal skin testing with 0.1 ml of vaccine along with a histamine and saline control may help to predict whether a type I event will occur with revaccination. Sensitized animals may exhibit wheal formation at the site of vaccine administration that is equal to or greater than that induced by the histamine injection.

If additional vaccine must be given in the future to a patient with a history of a mild type I reaction, pre-treatment with diphenhydramine 2.2 mglkg IM and rapid acting glucocorticosteroid 30 minutes prior to vaccination may prevent the urticarial/angioedema response. The patient should be hospitalized and observed for the day. If anaphylaxis has occurred, the best approach is to completely avoid ftrture administration of the offending vaccine to that patient.

Type II Hypersensitivity

Type II hypersensitivity is an immune-complex reaction associated with IgM and/or IgG antibody and mediated through activation of the classical complement cascade leading to direct cell mernbrane attack and lysis. Rarely. type II hypersensitivity may involve cell-mediated cytotoxicity.

Hematologic disorders (immune-mediated hemolytic anemia IIMHA] and immune-mediated thrombocytopenia IIIvlTP]) are the most common types of type II hypersensitivity reactions attribr-rted to small animal vaccination. If these disorders are vaccine-related. clinical signs usually appear r.vithin 3 weeks of vaccination. Other type II immune-complex disorders reported in association with vaccination include polyarthritis and polyner-rritis.

The pathophysiology behind these apparently vaccine-related irrmnne complex events is unclear. Sr-rggested mechanisms for this reactivity inciude: alterations of immunoregr-rlation by vaccination, non-specific immune activation by microbe-derived "superantigens". and molecular mimicry between autoantigens and vaccine antigens. Exposure to cross-r'eactive tissue protein in vaccine is another proposed mechanism of vaccine injLrry that has recently been investigated in cats. Preliminary experimental stlrdies show that residual proteins from virus cnlture on Crandall-Rees feline kidney cells remain in sufficient quantities in some feline parenteral vaccines to generate auto-antibody against normal feline kidney cells. What is not yet knorvn is whether these cross reacting antibodies are of any clinical relevance to the cat. Follow up at 56 weeks post-vaccination did not reveal any renal lesions in vaccinated cats. Horvever. I believe that it is yet another excellent reason to avoid overvaccinatioi-r of cats. Revaccination should be avoided in the future in patients with vaccine-related type II hypersensitivity diseases.

Type III hypersensitivity

Type III hypersensitivity results in large immune complexes that are deposited in the walls of blood vessels leading to immunologic attack and vascr"rlitis. These reactions are very slow to develop and clinical signs may not appear for several weeks following vaccination. The classic type III hypersensitivity reaction is the Arthr-rs vasculitis associated with canine adenovims I antigen that causes the "bhre eye" (corneal edema) reaction in dogs.

The most common type III vaccine-related event is post-vaccinal cutaneous vasclllopathy. This event is almost always associated with sr-rbcutaneous rabies vaccine administration. Histopathologic examination demonstrates an ischemic dermatopathy associated with vasculitis and panniculitis. Rabies antigen and complement can be demonstrated within vascular walls with immunohistochemical staining.

Cutaneous vasculopathy is r"rsr,rally seen in dogs and rarely in cats. The cutaneous vasculopathy lesions consist of weil-demarcated, often hyperpigmented areas of hair loss occuming at the vaccination site. Becar,rse it may take some time for the hair to epilate from the site, there may be a lag time of weeks to months after vaccination before clrtaneous vasculopathy lesions become apparent. If recognized early. it may be possible to stimulate hair regrowth by treating with pentoxyfylline at 25 mg/kg PO q12h and Vitamin E. Sr-rrgery may also be performed to remove the area of vasculitis-related alopecia. This problem can be prevented by avoiding the vaccine that induced the lesion.

Systemic vasculopathy/vasculitis is a rare but much more severe type III reaction. Because systemic vasculitis is a more recentiy recognized problem, there are few descriptions of this problem in the veterinary literature at the present time. Signs may include ear tip thrombosis and necrosis. blistering or ulcerative lesions at mlrcocntaneolrs junctions or areas at the conjunction of haired and non-haired skin. Orai mucous membrane and tongue ulceration, toenail and digital necrosis. footpad slor-rghing, and other skin lesions have also been observed. Systemic vascr-rlitis lesions usr-rally appear rvithin 2-3 u'eeks of vaccination. Diagnosis of systemic vasculitis/vasculopathf is made by biopsy of lesions to confirm the vasculitis.

Systemic vasculitis may be a life-threatening event. Treatment includes pentoxifylline and vitamin E as previor-rslv described for cutaneous vasculopathy. Additional therapy may inchrde t'luid. electrolyte. and nr-itritional support. Corticosteroids. other imrnr.rnoslrppressive drugs, antibiotics, gastric pl'otectants, and analgesics may be r-rsed depending on the severity and location of the lesions. Complete healing may take many r,veeks. Systemic vasculitis reactions are serious and should be considered potentially life-threatening. Prevention consists of avoiding any revaccination of the patient in the future. VACCINE.ASSOCIATED S ARCOMA

Vaccine-associated sarcomas (VAS) are corurective tissue tumors occurring at vaccination sites in response to chronic vaccine-induced inflammation. These neoplasms are highly malignant and very locally invasive. While the cat is definitely at highest risk for developing post-vaccinal sarcoma, vaccine site sarcomas have also been reporled in dogs, ferrets, rabbits, and horses. This serious and often fatal adverse vaccine event was first described in 1991 and concern about this problem led to the tormation of several panels and a national task force to study it further. In response to the reco-enition of VAS, in 2006 the American Association of Feline Practitioners issued recommendations for decreased frequency of vaccine administration, use of less reactive feline vaccines, and specific sites for vaccine administration in cats.

A genetic marker has been identified that may be related to neoplastic transformation at the site of chronic vaccine-induced inflammation in some cats althor-rgh a rnore recent study (Mucha 2012) found no association between VAS neoplasms and p53 SNP. In any case, genetics alone cannot explain the sudden appearance of VAS in cats all over the world in the mid- late-1980's, coincident with the introduction of adjuvanted vaccines.

The incidence of VAS in cats has been variably reported in the literature as between 1.3 per 1000 to I per 10,000 cats. Older cats (mean age 8-9 years) are more frequently affected and VAS has been seen in cats not vaccinated for more than 13 years suggestin-s that it may take many years for neoplastic development to become apparent in sorne cats. There is also evidence that older cats may develop a more severe inflarnmatory response to vaccine adjr-rvants than younger cats (Jelinek 2003).

VAS has been difficult to str-rdy because tunors may take years to develop, veterinarians change the vaccine products they nse, vaccination records may be incomplete. and the patient popr-rlation is highly mobile. The first pubiished retrospective review of VAS incidence (Kass JAVMA 2003) was limited by the small nr-rmber of animals r"rsed. the assumption that whatever vaccine was nsed the year the tumor developed was the initiating caLrse, and because non-adjuvanted recombinant vaccines had not been available long enou-sh to be critically evah-rated in the data analysis. Because VAS incidence is lorv, statistically valid prospective experirnental studies wor,rld require too many animals to be practical or ethical. Therefore. the exact etiopathogenesis and r.rnderlying mechanism for VAS development remains a controversial issue.

Nevertheless, vaccine adjuvant is knoi.vn to calise chronic injection site inflammation lasting at least 2 months post-injection (Day 2007). The United Kingdom (UK) Veterinary N'ledicines Directorate has had an adverse event monitoring system in place since 1984. A report of data analysis from this program demonstrated an increasing incidence of VAS frorn 1995 to 1999 with sarcomas occurring more frequently in cats receiving FeLV vaccine (adjr.rvanted) or other killed feline vaccines containing aluminum adjr-rvants. Rabies vaccines are not used in the UK. A recent review of VAS incidence and changes in site locations of VAS from 1990 to 2006 demonstrates a shift in the location of neoplasms from the interscapular area to the hind limbs. This shift in VAS location corresponds to changes in vaccination protocols to administer rabies and feline leukemia vaccines in the hind limbs of the cat recommended by the AAFP in 1996. In 1999, the World Health Organization classified veterinaly vaccine adjuvant as a class IIVIV carcinogen on the basis of their review of the literature on VAS.

The most recent epidemiologic study of injection site tumors (Srivastav JAVMA 2012) from the U.C. Davis research groLrp that published the initial epidemiologic study in 2003 in describing VAS from the hindlimbs [sites of FeLV and RV adrninistration using AAFP guidelines] now states: "Results consistently showed that case cats Ii.e. having VAS] were significantly less likely to have received recombinant vaccines than inactivated [i.e. adjuvanted] vaccines." Their further conclusion is that: "... the recombinant class of vaccines may potentially be less likely to induce sarcomas than inactivated vaccines...".

The Sarcoma Task Force developed the 3-2- I rule for evaluation of mass lesions at vaccination sites. If the lesion has been present for more than 3 months, if it is more than 2 cm in diameter, or is growing after one month, it should be biopsied! If histopathology reveals only inflammation, the mass should be completely excised with rvide margins. If histopathologic examination confirms neoplasia, the patient should be referred for definitive and radical treatment. Because VAS have tendrils of neoplastic cells that extend deeply from the primary lesion, effective treatment requires detailed imaging (CT or MRI) to define the exact extent of the neoplastic tissue, complete surgical excision with deep margins, and follow up radiation and/or chemotherapy. Prevention of VAS may involve avoiding inflammatory vaccines that can potentially induce neoplastic transformation in genetically predisposed catl;. Using the AAFP recommended vaccination sites will facilitate complete excision of a VAS shouid one occltr.

PRODUCT.RELATED E\-E,NTS

The major biologics rnanufacturers have highly controlled production processes and qr-ralit,v control systems to assllre the etficacy and safety of their products and direct prodr-rct-related adverse events are very rare. Some examples of product-related events include residr-rai vimlence of modified live vinrs vaccines or attenllated bacterins, interaction between viral vaccine components, contamination of canine vaccine with bluetongue virus. and rabies vaccine recall due to failure of efficacy in a longer duration of immunity study. Unfortunately, there is no way to predict or prevent product-related events. However, if such an event is suspected. it shor-rld be reported to the mannfacturer immediately.

LACK OF ININIUNOLOGIC RESPONSE TO VACCINES .\S AT\ ADVERSE EVENT

Most situations where vaccines fail to produce protective irnmr,rnity are not related to poor product efficacy but most often to improper vaccine handling or administration, or rhe inability of the host immune system to moLlnt an adeqr-rate immunologic response to the vaccine. Vaccines subjected to temperature variations or extremes during shipping and storage may lose potency. The administration of vaccines to ill or immunosuppressed patients may at best be ineffective and rarely may caLlse disease. MLV intranasal Llpper respiratory vaccines should not be administered to cats with retroviral infection (FeLV or FIV) because they can induce severe upper respiratory signs including oculonasal discharge and nasal or oral ulceration.

Animals that lack a certain lymphocyte subset or subsets that are critical for recognition and generation of a protective responsrl to a particular antigen are called non-responders or snb- optimal responders. These animals can be vaccinated repeatedly with highly efficacious vaccines but fail to be protected bi:cause they lack the genetic programming to respond. It is likely that these anirnals represent non-responders. We see fewer of these individuals now than in the past because we have rnore ,:fficacious canine parvovirus vaccines and because many non- responders that developed clinical parvovims disease died as a result and are no longer contributing to the gene pool.

ANTIBODY PRODUCTION ASi AN AD\'ERSE EVENT

In addition to the immune-mediated disease previor.rsly mentioned, there are other examples where the immunologic response t,f, vaccination may have a negative effect. In an experimental study, cats vaccinated rvith intranarsal feline coronavims vaccine (FIP vaccine) developed antibodies that caused antibody dependent enhancement of disease rvhen they were challenged with a pathogenic colonavims. More vaccinated cats died and they died more rapidly than unvaccinated cats in this study. Vaccination with the feline immr"rnodeficiency virus vaccine generates antibody that is indistinguishable fi'om natural infection. FlV-vaccinated cats will tesr positive with both ELISA and Western blot diagnostic tests for FIV for at least a vear post- vaccination confounding or,rr abilitll to determine whether they have true infection or not.

ADVERSE EVENT REPORTIN G

In order to properly report a sttspected adverse vaccine event. veterinarians must keep accurate patient records that inch-rde the product name. manufacttirer. lot and serial number, and the location of vaccine administration. AI1 sr-ispected events sholrld be repoited immediately to the prot-essional services hotline for the, vacciue rnanufacturer. If the patient is simultaneously given several vaccines prodr-rced by different manufacturers. it may be impossible to determine rvhich one may have caused the adverse er/ent. If an adverse event is confirmed. it should also be reported to the USDA adverse event reporting site: What to expect after your pet's vaccination

It is common for pets to experience some or all of the following mild side effects after receiving a vaccine, usualty starting within hours of the vaccination. If these side effects last for more than a day or two, or cause your pet significant discomfort, it is important for you to contact your veterinarian:

. Discornfort and local swelling at the vaccination site . Mild fever . Decreased appetite and activity . Sneezing, mild coughing, "snotty nose" or other respiratory signs may occur 2-5 days after your pet receives an intranasal vaccine

More serious, but less common side effects, such as allergic reactions, may occulwithin minutes to hours after vaccination. These reactions can be life- threatening and are medical emergencies. Seek veterinary care immediately if any of these signs develop:

a Persistent vomiting or diarrhea a Itchy skin that n"ray seem bumpy ("hives") a Swelling of the muzzle and around the face, neck, or eyes a Severe coughing or difficulty breathing a Collapse

A small, firm swelling under the skln may develop at the site of a recent vaccination. It should start to disappear within a couple r,veeks. If it persists more than three weeks, or seems to be geiting larger, you should contact your veterinarian.

Alurays inform your veterinarian if your pet has had prior reactions to any vaccine or medication. If in doubt, wait for 30-60 minutes foilowing vaccination before taking your pet home.

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