Rabies Challenge Fund: Five-Year DOI Study Results
Rabies vaccine is the one immunization required by law for domestic dogs and cats. It’s also the only one required to have duration of immunity studies for licensure in the United States. Until recently, annual or biannual revaccination for rabies was required by some states, even though nearly all USDA licensed rabies vaccines have a three-year duration, and there are no two-year licensed vaccines. Today, all states recognize the three-year revaccination standard, after completion of the initial two-dose series given within 12 months.
ADVERSE REACTIONS CAN BE SERIOUS, EVEN FATAL
Researchers believe this potent adjuvanted killed vaccine causes the most and worst adverse reactions in animals. Rabies vaccines are documented to elicit severe and even fatal reactions.
The clinical signs associated with vaccine reactions typically include fever, stiffness, sore joints and abdominal tenderness, susceptibility to infections, neurological disorders, seizures, encephalitis, collapse with auto-agglutinated red blood cells and icterus (autoimmune hemolytic anemia or AIHA), or generalized petechiae and ecchymotic hemorrhages (immune-mediated thrombocytopenia or ITP). Hepatic enzymes may be markedly elevated, and liver or kidney failure may occur by itself or accompany bone marrow suppression.
Post-vaccinal polyneuropathy is another recognized entity associated occasionally with the rabies vaccination. It can result in various clinical signs including muscular atrophy, inhibition or interruption of neuronal control of tissue and organ function, muscular excitation, un-coordination and weakness, as well as seizures.
A research study from Italy (Vascellari et al, 2003) documented cancerous tumors in 15 dogs at presumed sites of vaccine injection. Six of these dogs received rabies vaccines. In addition, vaccination of pet and research dogs with polyvalent vaccines containing rabies virus or rabies vaccine alone was shown to induce production of anti-thyroglobulin auto-antibodies, a provocative and important finding with implications for the subsequent development of hypothyroidism (Scott-Moncreiff et al, 2002).
ESTABLISHING THE RABIES CHALLENGE FUND CHARITABLE TRUST
The Rabies Challenge Fund Charitable Trust (RCF) was established in December 2005 by Co-Trustees Kris L. Christine of Alna, ME and W. Jean Dodds, DVM, of Hemopet in Garden Grove, CA. The mission of the Trust is to better define the duration of immunity conveyed by rabies vaccine in dogs. The eventual goal is to extend the legally required interval for rabies boosters to five and then seven years.
This vaccine research project is being performed by Dr. Ronald Schultz, Chairman of Pathobiology at the University of Wisconsin School of Veterinary Medicine. The study follows the strictly defined federal APHIS/USDA Title 9 standards for licensing rabies vaccines in concurrent five- and seven-year challenge trials. The funds are collected by Dr. Dodds, and are distributed annually by the Co-Trustees to the University of Wisconsin Foundation. The Foundation waived its usual 48% overhead charges for this research, so that the actual dollar amount donated goes directly to fund the project.
Contributions in time and effort to the RCF project by Dr. Schultz, the Co-Trustees, Hemopet, and web mistress Mimi Englander of Littleton, MA, are provided free of charge.
To date, funds have been sent to the University of Wisconsin Foundation for five years of the study – $175,000 for each of the first two years, $150,000 for year three, and $145,000 for years four and five. We are continuing to raise the needed funds to complete years six and seven, and look forward to the results of the remainder of this study, which should benefit all dogs everywhere.
SUMMARY OF FIVE-YEAR DURATION OF IMMUNITY STUDY
The first rabies vaccine studied was selected based on the superior response it provided in the USDA challenge trials for licensing. Another licensed rabies vaccine was administered to a second, separate group of dogs two years after the first study began, so that a minimum of two commercially available rabies vaccines would be tested.
The second vaccine selected is the one currently administered to a very high percentage of dogs. Both vaccines demonstrated excellent protection based on antibody testing for each of the first three study years. However, fewer than 30% of dogs in the first vaccine group, now five years since vaccination, had serum rabies antibody titer levels considered positive on the Rapid Fluorescent Focus Inhibition Test (RFFIT) (above the 0.1 IU/mL level stated by the Centers for Disease Control to protect a person from rabies).
Some of the dogs with low or no detected RFFIT antibody were further tested to determine if they had “immunologic memory”. This in vitro test shows whether memory is present or not, even in cases when serum antibody cannot be detected at a level considered to be protective. The results of this further testing indicated that most of the dogs vaccinated five years ago, even without a positive RFFIT, do have “immunologic memory”. As soon as a USDA licensed facility can be reserved, we plan to challenge some of those dogs with rabies virus to determine if the memory response demonstrated actually correlates with protection.
Our conclusion from studies with the initial rabies vaccine is that the immunity conferred by that product, and assessed by the in vitro RFFIT, was excellent for the first three years, then declined during the fourth year, and continued to drop during the fifth. Nevertheless, the dogs that completed the five-year study who were given a second rabies vaccine (even those with rabies antibody titers that dropped below the RFFIT positive level), demonstrated boosted rabies titers, indicating the presence of an active immune memory cell response. The second vaccine group, which is now three years from vaccination, will remain on study for at least two more years.
Principal investigator, Dr. Ronald Schultz, is preparing results of the study and details described above for scientific peer review and publication. That data will be made available to the public as soon as our paper has been accepted for publication.
The Rabies Challenge Fund Charitable Trust is a 501(c)(3) charitable organization (Fed. EIN # 84-6390682).