Vaccination: An overview (Proceedings)

Vaccination is an important tool in veterinary medicine, preventing disease and reducing virus circulation for many important viral pathogens. In small animal medicine, vaccines for a multitude of agents are available, and the decisions regarding what vaccines to use and how often to use them can be difficult to determine. This discussion will cover the various general types of vaccines available, and summary of recommended guidelines for selection.

Vaccines are designed to enhance the specific immune response to a particular pathogen in order to prevent disease upon exposure and natural infection. This is accomplished through inoculation with all or part of an organism. The development of a vaccine must take into consideration the type of immunity needed, the role of memory cells, safety, cost, stability, and ease of administration. Vaccine types can be divided into two basic categories: noninfectious and infectious.

Noninfectious vaccines

These vaccines include killed whole virus, or inoculum containing one or more virus peptides or proteins. The former is produced by inactivation of virus propagated in cell culture or eggs through chemical modification or other means. The latter, also referred to as subunit vaccines, may be produced in a variety of ways, including viral protein extraction and purification, recombinant production of virus protein, or peptide synthesis. In all cases, noninfectious vaccines require an adjuvant to enhance the immune response, since there is no virus replication following inoculation. This lack of replication also means that, by necessity the antigen load in noninfectious vaccines is higher than that of infectious vaccines.

Noninfectious vaccines have certain advantages. There is no chance of reversion to virulence since the virus is "dead". These vaccines are generally stable, and safe; thus they can be used in debilitated or pregnant animals with minimal risk. However, because there is no active replication, the response stimulated is primarily humoral, with little if any cell-mediated component. The duration of immunity tends to be shorter than that of infectious vaccines, and multiple boosters are often required. Because of the addition of adjuvant, and the relatively high antigenic mass, adverse reactions may be more common, including hypersensitivity reactions and granuloma formation. Examples in small animal medicine include most rabies vaccines, and most bacterins.

Infectious vaccines

Infectious, or live vaccines contain viable, replicating organisms. These organisms have been modified in some way that reduces or eliminates their disease-producing capabilities while maintaining their antigenicity. The majority of infectious vaccines are attenuated whole viruses, containing the relevant pathogen which has undergone multiple mutations designed to abolish its pathogenicity. Newer vaccines use recombinant technology, including vector viruses or DNA plasmids that express immunogenic viral proteins. Recombinant vaccines are currently available, and most use a canarypoxvirus as the vector for various virus proteins such as the coat proteins of canine distemper virus and rabies virus.

Infectious vaccines have a lower antigenic mass, and require no adjuvant. Because of their replicative ability, these vaccines stimulate both humoral and cell-mediated immunity, and generally fewer boosters are required to induce and maintain protection. There is some, albeit low risk for reversion to virulence. Contamination of live vaccines with adventitious agents has rarely occurred leading to serious consequences. Generally, infectious vaccines are of lower stability and require maintenance of the cold chain. Many are freeze-dried, and once rehydrated, have a short period of viability. Because the agents are infectious, there is some risk for immunosuppressed animals, and significant risk for the fetus in pregnant animals.

Vaccine selection

In considering which vaccines to use, one must consider not only the epidemiology and threat of a particular pathogen, but also the chances of the individual animal to exposure, and the properties of the vaccines available, including safety, efficacy and cost. Many vaccines are multivalent, necessitating only a single inoculation to induce immunity to multiple agents. While no concensus exists, guidelines are available from various professional organizations, including the AVMA, ACVIM, and AAFP.

Vaccination of the young begins at 6-8 weeks of age. Multiple boosters are given because maternal immunity interferes with vaccinal response. Because one doesn't know the level in each animal for each pathogen at each time point (and it is not feasible nor cost-effective to measure this), repeated boosters are given until the point when maternal immunity has likely decreased sufficiently to allow induction of immunity, usually at 16-18 weeks of age. Most vaccines are given subcutaneously. Recently, intradermal vaccines have been developed in cats in an attempt to reduce the likelihood of neoplasia development. This inoculation route has been used in human medicine for some time, and has proven to be efficacious in cats. Mucosal vaccines (primarily intranasal) are also available for some pathogens, and effectively induce local immunity at the mucosal surface.

Vaccine failures can occur. This may be due to host factors, such as immunosuppression, the presence of maternal immunity, and genetics of the animal. Vaccine factors, such as administration by an inappropriate route and antigenic variation of the pathogen, may also occur. Finally, human error including improper storage, preparation, and administration may lead to problems.

Adverse reactions have also become a major concern in small animal medicine. Errors in manufacture are a rare complication, but can occur; thus adverse reactions should be reported to the manufacturer as well as the USDA. Errors in administration can also occur, such as mistakenly giving an intranasal vaccine parenterally. These can potentially be serious, and may require treatment. Most commonly, animals experience a typical response of lethargy, fever, and inappetance. This is generally short-lived, and self-limiting. More concerning are inappropriate responses of the animal to the vaccine. These fall into two general categories. The first is immediate hypersensitivity. This may be a local or systemic response, and is due to pre-existing antibody to the agent. This is the classic "allergic reaction" to the vaccine and can be life-threatening. The second is a delayed response, requiring days of longer to develop. The vaccine, seen as foreign, elicits a significant inflammatory response and is especially true for adjuvanted vaccines. This response can manifest as a granuloma, or more seriously, a fibrosarcoma . The precise mechanism of vaccine-induced sarcoma remains unclear, but appears to be a direct consequence of vaccination. Luckily, these are the exception rather than the rule, but can have serious consequences; in cats, adjuvanted vaccines are not routinely recommended. The likelihood of adverse reactions in dogs has been found to correlate with the size of the dog and the number of inoculations given, with higher risk associated with small size and multiple inoculations. Less clear is the link of vaccines with immune-mediated disease such as hemolytic anemia – current scientific data has not established a cause and effect relationship. Future research may shed light on whether an association, other than temporal, exists.

References

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Day, MJ. 2006. Vaccine Side Effects: Fact and Fiction. Vet Micro, 117:51-58.

Grosenbaugh, Deborah A., Tim Leard, M. Camila Pardo. 2006. Protection from challenge following administration of a canarypox virus–vectored recombinant feline leukemia virus vaccine in cats previously vaccinated with a killed virus vaccine. JAVMA, Vol 228, No. 5, March 1, 2006, 726-727.

Moore, George E., Lynn F. Guptill, Michael P. Ward, Nita W. Glickman, Karen K. Faunt, Hugh B. Lewis, Lawrence T. Glickman, Adverse events diagnosed within three days of vaccine administration in dogs. JAVMA, Vol 227, No. 7, October 1, 2005 1102-1108.

L. J. Larson, T. L. Hageny, C. J. Haase, R. D. Schultz 2006. Effect of Recombinant Canine Distemper Vaccine on Antibody Titers in Previously Vaccinated Dogs. Veterinary Therapeutics Vol. 7, No. 2, Summer 2006 107-112.

L. J. Larson, R. D. Schultz. 2006. Effect of Vaccination with Recombinant Canine Distemper Virus Vaccine Immediately before Exposure under Shelter-Like Conditions. Veterinary Therapeutics • Vol. 7, No. 2, Summer 2006 113-118.

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