Veterinary Medicine - December 2007 - (Page MerialA)

Immunology Bulletin Feline vaccinations and adjuvanted vaccine By Richard B. Ford, DVM, MS, DACVIM, DACVPM (HON), and Alice M. Wolf, DVM, DACVIM, DABVP Rabies vaccine should be administered on the right hind limb, as distally as possible; feline leukemia vaccine should be administered on the left hind limb, as distally as possible.1* These were the vaccination site recommendations of the Vaccine-Associated Feline Sarcoma Task Force (VAFSTF) published in 2001—recommendations that are still in place today even though VAFSTF was discontinued in July 2005. Yet, VAFSTF never addressed the specific reason for the recommendation that rabies and feline leukemia vaccines be administered as distally as possible. Unfortunately, current inoculation site recommendations are based on facilitating the removal of a vaccine-associated sarcoma by amputating the patient’s leg. This is hardly an acceptable solution to what is now recognized as the most significant adverse event associated with feline vaccination. So, the ultimate question regarding vaccine-associated sarcoma remains: What can be done to mitigate the risk of vaccine-associated sarcoma in cats? Some mechanisms include forming a repository of antigen in tissue (prolonged exposure), facilitating the targeting of antigen presenting cells, and stimulating macrophages to induce activation of lymphocytes.3 In fact, it’s reasonable to assume that multiple mechanisms may be involved with any one adjuvant. Furthermore, while one adjuvant may be efficacious for some vaccines, it may be totally inadequate for others.4 The link to tumorigenesis A protective immune response ideally destroys invading pathogens. In the process, tissue damage may result (e.g., immune-mediated vasculitis). By its ability to enhance the immune response, adjuvant may actually augment the adverse effects of a vaccine.5 Toxicity associated with adjuvants is believed to increase with potency.2 In the development of an adjuvanted vaccine, maximizing the immunogenic effects of antigen while minimizing the adverse consequences of adjuvant becomes a critical factor. While any vaccine carries potential for inducing an adverse reaction in any patient, the potential for vaccine-associated sarcoma in cats is among the most serious. In 1993, a causal relationship between vaccination with adjuvanted rabies vaccine and adjuvanted feline leukemia vaccine was established.6 With an estimated incidence of one to 10 cases per 10,000 vaccinates,1 the true incidence of vaccine-associated sarcoma is not known. There is no definitive study that proves adjuvant causes cancer in cats; however, the evidence is compelling. In 1985, the modified-live (nonadjuvanted) rabies vaccine was replaced in the United States with a killed, adjuvanted rabies vaccine. Also in 1985, the first feline leukemia vaccine, a killed, adjuvanted product, was licensed. Both of these vaccines were used extensively throughout the United States. In the late 1980s, the University of Pennsylvania School of Veterinary Medicine reported an increase in inflammatory vaccine-site reactions, which corresponded with 1987 state legislation requiring vaccination of cats against rabies. Interestingly, the first The role of adjuvant in vaccine The use of an adjuvant to enhance an immune response to an antigen dates to the 1920s during attempts to immunize horses against diphtheria and tetanus. Co-injecting vaccine antigen with things like tapioca and agar caused abscesses, which in turn resulted in higher antibody titers. Soon afterward, aluminum salts** and Freund’s complete (and incomplete) adjuvants were developed for use in human and animal vaccines. In addition to aluminum salts, an impressive spectrum of adjuvant classes exists: calcium salts, oil emulsions, liposomes, saponins, immune-stimulating complexes, bacterial products, and CpG DNA motifs, to name a few. The list of compounds having adjuvant activity numbers in the hundreds.2 It is well known that killed bacterial and viral antigens are especially poor immune stimulants. Adding an adjuvant to a killed antigen enhances the immune response. Despite widespread use of adjuvanted vaccines today, the exact mechanism through which an adjuvant actually promotes an enhanced immune response is largely unknown. ** Aluminum adjuvants are the only ones approved for human use. Supported by Merial www.Merial.com http://www.Merial.com http://www.Merial.com

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Veterinary Medicine - December 2007 Contents Letters Editors' Guest Thanking Our Valued Reviewers The Veterinary Medicine Interview: Dr. Joseph Harari Clinical Exposures Idea Exchange Answers to Three Commonly Asked Questions About Lyme Disease Practical Ideas for Managing Common Internal Medicine Problems A Tip for Interpreting Leptospira Species Titers Investigating Proteinuric Kidney Disease Counseling New Puppy Owners: Normal Play vs. Aggressive Tendencies 11 Guidelines for Conservatively Treating Chronic Kidney Disease CE Form Product Preview Advertiser Index Marketplace/Classifieds Mind Over Miller Merial Insert

Veterinary Medicine - December 2007

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