Vaccines–what choice do I have? (Proceedings)

Immunoprophylaxis is the enhancement of a specific immune response to the specific pathogen. Humoral and cell-mediated immune response are critical to effective immunity. This response is induced by microbes, their components or by-products. The majority of vaccines prevent infectious disease, but not infection.

Vaccinate with what? There are a number of options that fall into two basic categories: passive immunization and active immunization. Selection depends upon the situation. Passive immunization involves the transfer of specific antibodies from one individual to another. The best example of this is maternal immunity. Passive immunity is immediate, and is good for poor immunogens. Disadvantages are the possibility of allergic reactions to the serum; protection is short-lived; and it delays ability to vaccinate.

Active Immunization involves stimulating the host with all or part of an organism. Vaccine design must consider the immune response needed: humoral vs. cellular. Vaccine design must consider role of memory cells: short vs. longer incubation. And the ideal vaccine should be inexpensive, stable, adaptable to mass vaccination, and confer strong and long lasting immunity with no or minimal side effects.

Noninfectious vaccines may contain inactivated or killed pathogen; the key is it does not replicate in the host. It may be a whole organism, or a piece of the organism, which includes subunit vaccines, recombinant protein vaccines, and peptide vaccines. Noninfectious vaccines generally require adjuvant, which increases the duration and amount of immunostimulation; mechanisms for most are poorly understood. Adjuvants can cause local reactions. In addition, noninfectious vaccines stimulate primarily a humoral response and generally require multiple inoculations. With noninfectious vaccines, there is no possibility of reversion to virulence, and they are stable and safe; they are ideal for pregnant, debilitated, or immunosuppressed individuals.

With live vaccines, the pathogen is modified so that it loses its virulence while retaining its ability to replicate in the host and its immunogenicity. Initial antigenic content is lower than with inactivated vaccines and generally no adjuvant is required. Importantly, live vaccines effectively stimulate both humoral and CMI, and a single inoculation may be effective. Options include attenuated whole organisms – these usually involve multiple mutations. Others include recombinant vectors and naked nucleic acids. For the former, viruses or bacteria are used as carriers to express antigens of other pathogens- insertion of genes for protective antigens into genome of another agent. The vector expresses the inserted gene, stimulating humoral AND CMI. Viruses (vaccinia, canarypox, adenovirus) and bacteria (Salmonella, BCG) may be used. The latter are generally DNA of the relevant genes of a pathogen that is taken up by muscle cells and expressed; again, both humoral and CMI are stimulated; in addition, these may be even safer in immunocompromised hosts than live vector vaccines.

With both of these alternatives, the vaccines can be engineered such that maternally derived antibody does not interfere. Immunity with live vaccines is generally long-lasting, and a single inoculation is usually effective. Lower antigenic mass is required, and no adjuvant is required. There is a possibility of reversion to virulence, though this is very uncommon. Generally, live vaccines are of lower stability and require maintenance of the cold chain. Potentially, they are a risk to immunosuppressed animals or to animals in utero.

In designing vaccination programs, vaccine properties, including efficacy, potential for adverse reactions, and cost must all be considered. Also important are the pathogen's epidemiology and the risk of the animal to exposure to the agent, as well as the severity of disease. Thus, how is a vaccine selected is based on need, efficacy, safety, and cost.

Vaccine failures which may be due to host factors: the presence of pre-existing immunity, immunosuppression, or genetics of the animal and its ability to respond. Vaccine factors may include route of administration, vaccine design, and antigenic variation of the pathogen. Human error is also possible: improper selection, storage, preparation, or administration. adverse reactions to a vaccine are also possible, and are a concern in small animal medicine. An adverse event is any undesired or unintended effect, including lack of response, or any sensitivity, injury or toxicity associated with use of a vaccine, regardless of whether the event can be directly attributed to the vaccine. Young animals are more likely to have lack of efficacy.

Hypersensitivity reactions (type I) most common in young (incidence peaks at ~2 years of age) and small breeds. Immune-mediated disease is sometimes observed following vaccination, including ITP, IMHA – type II hypersensitivities; vasculitis, dermatitis (rabies), polyarthritis – type III hypersensitivities. This is a temporal association and causation is not proven; mechanism unclear for most. VAS in cats is secondary to inflammation at injection site and is associated with adjuvanted vaccines or repositol injections. One should avoid multiple injections at a single site, and avoid adjuvanted vaccines in cats. It is important report any adverse eventto manufacturer and Center for Veterinary Biologics: (http://www.aphis.usda.gov/animal_health/vet_biologics/vb_adverse_event.shtml)

References

McVey, S., and J Shi. 2010. Vaccines in Veterinary Medicine: A Brief Review of History and Technology. VCNA, 40(3):381-392.

McVey, D. S., and M. A. Kennedy. 2008. Vaccines for Emerging and Re-Emerging Viral Diseases of Companion Animals. VCNA, 38(4):903-918.

Patel,J. R., and J.G.M. Heldens. 2009. Review of companion animal viral diseases and immunoprophylaxis. Vaccine, 27:491-504.

Shams, H. 2005. Recent developments in veterinary vaccinology. Vet J, 170:289-299.

Bowersock, T. L., and Stephen Martin. 1999. Vaccine delivery to animals. Adv Drug Delivery Rev, 38:167-194.