The challenge to produce effective and safe vaccines for the prevalent infectious diseases of humans and animals has become increasingly difficult. In veterinary medicine, evidence implicating vaccines in triggering immune-mediated and other chronic disorders (vaccinosis) is compelling. While some of these problems have been traced to contaminated or poorly attenuated batches of vaccine that revert to virulence, others apparently reflect the host's genetic predisposition to react adversely upon receiving the monovalent of polyvalent products given routinely to animals. Animals of certain susceptible breeds or families appear to be at increased risk for severe and lingering adverse reactions to vaccines.

The onset of adverse reactions to conventional vaccinations (or other inciting drugs, chemicals , or infectious agents) can be an immediate hypersensitivity or anaphylactic reaction, or can occur acutely (24-48 hours afterwards), or later on (10-30 days) in a delayed type immune response usually caused by immune-complex formation. Typical signs of adverse immune reactions include fever, stiffness, sore joints and abdominal tenderness, susceptibility to infections, central and peripheral nervous system disorders or inflammation, collapse with autoagglutinated red blood cells and jaundice, or generalized pinpoint hemorrhages or bruises. Liver enzymes may be markedly elevated and liver or kidney failure may accompany bone marrow suppression. Furthermore, recent vaccination of genetically susceptible breeds has been associated with transient seizures in puppies and adult dogs, as well as a variety of autoimmune diseases including those affecting the blood, endocrine organs, joints, skin and mucosa, eyes, muscles, liver, kidneys and bowel. The underlying genetic basis of these conditions places other littermates and close relatives at increased risk.

Vaccination also can overwhelm the immuno-compromised or even healthy host that is repeatedly bombarded with other environmental stimuli and is genetically predisposed to react adversely upon viral challenge. The recently weaned young puppy or kitten entering a new environment is at greater risk here, as its immature immune system can be temporarily or more permanently harmed. Consequences in later life may be the increased susceptibility to chronic debilitating diseases.

As combination (polyvalent) vaccines contain antigens other than the clinically important infectious disease agents, some may be unnecessary, and their use may increase the risk of adverse reactions. Today's licensed leptospirosis bacterins afford little, if any, protection against the clinically important field strains, and the antibodies they elicit last only a few months. Other vaccines, such as for Lyme disease, may not be needed because the disease is limited to certain geographical areas. Annual revaccination for rabies is required by some states even though USDA licensed rabies vaccine have a 3-year duration. Thus, the overall risk-benefit ratio of using certain vaccines or multiple antigen vaccines given simultaneously and repeatedly should be reexamined. It must be recognized, however, that the luxury of asking such questions today is presented only because the risk of disease has been effectively reduced by the widespread use of vaccination programs.

Given this troublesome situation, what are the experts saying about these issues? In 1995 a landmark review commentary focused the attention of the veterinary profession on the advisability of current vaccine practices. Are we over-vaccinating companion animals, and if so, what is the appropriate periodicity of booster vaccines? Discussion of this provocative topic generally leads to other questions about the duration of immunity conferred by the currently licensed vaccine components.

In response to questions posed in the first part of this article, veterinary vaccinologists have recommended new protocols for dogs and cats. These include: 1) giving the puppy or kitten vaccine series followed by a booster at one year of age; 2) administering further boosters in a combination vaccine every three years or as split components alternating every other year until; 3) the pet reaches geriatric age, at which time booster vaccination is likely to be unnecessary and may be unadvisable for those with aging or immunologic disorders. In the intervening years between booster vaccinations, and in the case of geriatric pets, circulating humoral immunity can be evaluated by measuring serum vaccine antibody titers as an indication of the presence of "immune memory". This latter phrase is more correct that "protective immunity", because protection against disease means survival after challenge with the infectious agent and may not correlate with the serum antibody titer. Titers do not distinguish between immunity generated by vaccination or exposure to the disease, although the magnitude of immunity produced by vaccination is usually lower. Except where vaccination is required by law, animals that previously experienced an adverse reaction to vaccination or are at genetic or physiological risk for such reactions also can have serum antibody titers measured annually instead of revaccination. If adequate titers are found, the animal should not need revaccination until some future date. Rechecking antibody titers can be performed thereafter, or can be offered as an alternative to pet owners who prefer not to follow the conventional practice of annual or semiannual vaccination. Reliable serologic vaccine titering is available from several university and commercial laboratories and the cost is reasonable.

Relatively little has been published about the duration of immunity following vaccination, although new data are beginning to appear. In Sweden, an in-depth study found adequate titers against canine distemper virus (CDV) in 83% of a very large group of dogs vaccinated more than 4 years beforehand. Another recent study of dogs vaccinated 9-55.5 months previously found 73% of 122 dogs to have protective canine parvovirus (CPV) titers, and 79% of 117 dogs to be adequately protected against CDV. The authors concluded that annual revaccination should be maintained because less than 90% of those vaccinated reached their criteria for protective titers. However, using similar criteria to assess vaccine antibody titers in a much larger groups of dogs, we came to a different conclusion (Twark and Dodds, JAVMA, in press, 2000). Our study evaluated 1441 dogs for CPV antibody titer and 1379 dogs for CDV antibody titer. Of these, 95% were judged to have adequate CPV titers, and 98% had adequate CDV titers. Vaccine histories were available for 444 of the dogs in which CPV titers were determined; 433 of them also had CDV titers measured. The interval between last vaccination and titering ranged from 1 month to 7 years, with the majority (625) being between 1-2 years. On the basis of our data, we concluded that annual revaccination is unnecessary in most cases.

A multifaceted approach to furthering the recognition of this situation, along with alternative strategies for containing infectious diseases and reducing the environmental impact of conventional vaccines is clearly needed. As a beginning we can increase the interval between adult booster vaccinations from one to three years, except as required by law, and monitor serum antibody levels for assessing immune memory response to the clinically important infectious agents.

W. Jean Dodds, DVM is the Founder and President of HEMOPET. Hemopet specializes in veterinary transfusion medicine, effective blood substitutes, bone marrow and tissue banks.

Jeans'goal for the 2000's is to form other regional centers and consolidate the national program.

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