Introduction

Medical decisions concerning vaccine selection and administration protocols are among the most complicated medical decisions facing veterinarians today. The reasons are numerous and include, but are not necessarily limited to 1) continual changes in our understanding of the immune system; 2) changes in local/regional population susceptibilities to various diseases; 3) increased animal valuation with related liabilities; 4) longer animal life expectancies; and 5) improved medical record systems which allows for better tracking of the short, medium, and long-term effects of vaccine use/administration. Other contributing factors include improved, 1) understanding of infectious diseases; 2) knowledge of the biologic regulatory licensing/labeling, and 3) awareness of potential risks associated with vaccine use/administration.

COBTA has studied the issues of veterinary vaccinology and immunology, including a review of the scientific literature with interactive testimony of experts from academia, veterinary vaccine manufacturers, state/federal governments, and veterinary private practice. Topics included safety, efficacy, duration of immunity, research and development of vaccines, vaccine licensing, product labeling, adverse events, adverse event reporting, governmental oversight of manufacturers, and legal issues associated with medical procedures.

Vaccines have played a significant role in enabling people and animals to live longer and healthier lives in this world filled with microbial pathogens. Vaccine products vary in efficacy and safety and are not necessarily indicated for all patients. Modern science continues to develop strategies and technologies for safer and more efficacious vaccines. Consequently, thorough evaluations of the potential for disease exposure, individual patient susceptibility to various diseases, and the risks/benefits associated with vaccination, are necessary in order to establish optimal health care programs for each individual patient.

Conclusions
COBTA concludes there are insufficient data available to scientifically determine a single best vaccination protocol regimen for application to all animals globally. Despite significant advances in our knowledge of antigens and antigen presentation, gaps still remain in our understanding of the immune system's acute and chronic reaction to multiple vaccinations. The body of knowledge surrounding the genetic variability within individual breeds or species and the resulting idiopathic responses to vaccination (including vaccine-associated adverse reactions), is increasing but remains too inconclusive to make specific recommendations appropriate for all patients. Consequently, COBTA believes that a customized approach to recommended vaccination protocols is the safest and most effective method to medically address the increasing diversity in patients presented for immunization.

Under a veterinarian-client-patient relationship, the practitioner and client must determine the best patient care programs for implementation. Since our knowledge base is constantly evolving, vaccination decisions require a thorough and ongoing review of scientific information and expert opinion in order to appropriately customize vaccine recommendations for individual animal patients.

The one-year revaccination recommendation found on many vaccine labels is often based on historical precedent and was allowed by USDA regulation since it was based on the best scientific knowledge available at that time, which did not necessarily include product specific data. Even in those cases where scientific data were submitted to qualify a revaccination label claim, the data generally targeted a minimum duration of immunity and did not necessarily resolve the question regarding average or maximum duration of immunity.

Vaccination is a potent medical procedure with both risks and benefits. While there is evidence that some vaccines provide immunity beyond one year, revaccination of patients with sufficient immunity does not necessarily add to their disease protection and may increase the potential risk of post-vaccination adverse events.

Serologic titers may not accurately predict immunity from disease. With respect to many infectious diseases, it is not currently possible to determine the immune status of an animal without assessing response to challenge. Due to the emergence of newer and improved antibody tests, serological assays are being used to determine immune status and establish vaccination protocols for animal patients. Caution should be exercised to make sure that serological titers have been clinically correlated to host-animal protection for the specific disease and species being tested.

Adverse events may be associated with the antigen, adjuvant, carrier, preservative, or a combination thereof. Possible adverse events include, but are not necessarily limited to, failure to immunize, anaphylaxis, immuno-suppression, autoimmune disorders, transient infections, long-term infected carrier states, and local development of tumors. The role of genetic predisposition to adverse events needs further exploration and definition.

Vaccine program goals include providing optimal immunity against clinically relevant diseases the patient is at-risk to contract, while minimizing the potential for adverse events.

Multiple sources of information can be of value to practitioners in their review of vaccines and infectious diseases, including scientific data and opinion from experts, species and specialty groups, manufacturers, and government agencies. For example, the American Animal Hospital Association and American Association of Feline Practitioners have produced extensive documents giving specific recommendations for companion animals. All sources of scientific information and expert opinion need to be carefully and critically considered to properly prepare the customized vaccine programs animal patients require.

Principles and Practice of Vaccination

Vaccine Application:
The proper application of vaccines to animal populations has enhanced their health and welfare, and prolonged their life-spans. The risks to animal health from non-vaccination are significant.

The goal for a vaccination program is to prevent disease and thereby promote optimal patient, herd, and/or public health.

Unnecessary stimulation of the immune system does not necessarily result in enhanced disease resistance, and may increase the potential risk of post-vaccination adverse events.

Disease carriers, including animals that shed infectious agents but do not necessarily show signs of illness, are sources of infection for susceptible animals. Sufficient immunity within a population of animals is an important component of preventing disease prevalence. Programs targeting immunization of susceptible animals are critical to disease control.

Vaccination protects a population of animals by providing a level of resistance to a disease in those individual patients that are able to respond. Vaccination does not protect every individual patient even when they are properly vaccinated.

There is a critical need for more fully developed, scientifically based, and statistically valid evaluation of vaccine products to provide practitioners with a basis for developing vaccination programs that maximize benefits and minimize associated risks for the patients under their care.

Vaccination is a potent medical procedure associated with both benefits and risks for the patient. Adverse events, including some that are potentially severe, can be unintended consequences of vaccination.

Vaccine Administration

Information about the benefits and risks of vaccination are important to practitioners, owners, and the general public. Appropriate decisions concerning individual vaccine selection and vaccination program choices are best made under veterinarian-client-patient relationships.

Vaccines, including polyvalent products, should be selected to include only those antigens appropriate for the specific risk needs of the patient, thereby eliminating unnecessary immune system stimulation and thus lowering potential risks of adverse events. Veterinarians need to be aware of the risk of "endotoxin stacking" with the use of multiple Gram-negative vaccines.

Knowledge of immunology and vaccinology, including associated benefits and risks, and the pathobiology of infectious diseases, are necessary to implement an effective vaccination program. Consideration of exposure, susceptibility, potential severity of disease, vaccine efficacy and safety, related state/federal restrictions, the potential for public health concerns, and owner's preferences are essential components of a customized vaccination program.

Those veterinarians with an established veterinarian-client-patient relationship are in the best position to make recommendations customized to the needs of the individual patient(s) and owner/client.

Revaccination recommendations should be designed to maintain clinically relevant immunity while minimizing adverse event potential.

Additional information, including vaccine-specific scientific data on minimum, average, and maximum duration of immunity is desired to craft optimal revaccination recommendations.

Veterinarians should create a core vaccine program, intended for use in the majority of animals in their practice area. Core vaccines are those that protect from diseases that are endemic to a region, those with potential public health significance, required by law, virulent/highly infectious, and/or those posing a risk of severe disease. Core vaccines have clearly demonstrated efficacy and safety, and thus exhibit a high enough level of patient benefit and low enough level of risk to justify their use in the majority of patients.

Veterinarians should create a non-core vaccine program, intended for a minority of animals in their practice area. Non-core vaccines are those that fit any of the following criteria:

• Targeted for diseases that are of limited risk in the region
• Protects against diseases that present less severe threats to infected patients
• Have a benefit/risk ratio that is too low to justify the use of the product in all circumstances
• Lacks adequate scientific information to fully evaluate the safety and/or efficacy of the product

Multiple-dose Vials

There are numerous advantages associated with the use of single dose vials. If multiple dose vials are used, care must be taken to thoroughly mix vaccine contents and administer the recommended dose according to the product label. Appropriate measures should be taken to minimize the potential for vaccine contamination with extraneous microbes or chemicals.

Regulatory Issues

The vaccine performance claims made by the manufacturers of USDA-licensed products have been substantiated by a variety of testing methods. Careful evaluation of labels and other information is necessary to compare and contrast between the available products. USDA-licensed products should be used if possible.

Current adverse event reporting systems need significant improvement in the capture, analysis and reporting of adverse events. Practitioner commitment to adverse event reporting, and timely access for practitioners to current analysis of adverse event data, are essential to providing optimal patient care.

There is potential legal liability for all medical procedures including vaccination.

Vaccine Licensing and Labeling:
Biological agents are regulated by USDA, not FDA, and thus are not subject to FDA regulations that address extra label use. It is generally recommended to follow label instructions, however, in most cases veterinarians may legally use vaccines in a discretionary manner if medically justified and in compliance with State/Federal restrictions that apply.

USDA licensing at the full approval level provides a baseline standard for efficacy, safety, purity, and potency, but the clinical need (relevancy) or usefulness (applicability) of a product may not be completely assured by the licensing process. In some instances, the number of animals used in pre-license safety testing might be inadequate to identify rare but relevant safety concerns. In other instances, product efficacy and/or safety can be impacted by the use of concurrent therapeutic approaches that may not be cited as a contraindication or warning on the product label.

The USDA must approve labels for biological products. However, current labels frequently contain revaccination interval recommendations based on historical precedence and acceptance rather than specific duration of immunity data; consequently, some product labels may fail to adequately inform practitioners about optimal revaccination and long-term use of a product. Newer products and some older products with updated labels have revaccination recommendations based on data on file with USDA.

Labels on licensed vaccines make different claims and should be carefully studied when evaluating products. Claims may, for example, declare the product (a) prevents infection, (b) prevents disease, (c) aids in disease prevention, (d) aids in disease control (reduce disease severity, duration, and/or onset), or (e) other (control of infectiousness through reduction of pathogen colonization and/or shedding in animals). Each of these claims represents a different level of performance outcome that might be important in selection of a specific vaccine.

USDA approved products, under conditional licensure, have demonstrated host-animal safety and a reasonable expectation of efficacy. Autogenous vaccine regulations do not require confirmation of 1) efficacy, 2) potency correlated to efficacy; or 3) host-animal safety to the USDA prior to product licensure and use.