Who hasn’t cried at the ending of Old Yeller? (Well, I haven’t because I was only four when Disney re-released the classic film in 1965, but I’m sure I would have.)
Although I was too young to see the film, of course I know the story of the beloved dog felled by the bite of a rabid wolf. Humans have feared rabies for millennia. The viral disease was fatal until Louis Pasteur and Emile Roux developed a vaccine against it in 1885.
Thanks to the vaccine, millions of pets are protected from infection and from spreading the virus (according to the Centers for Disease Control, only 8.4 percent of the rabid animals reported in 2012 were domestic animals), but it has a down side. Because rabies is fatal and is a zoonosis, meaning it can be transmitted between animals and humans, rabies vaccination of dogs is required by laws in all states (many but not all states also require vaccination of cats). Because rabies vaccines are licensed for only one and three years, pets receive multiple rabies vaccinations over their lifetime.
While many states have moved to a triennial requirement for the rabies vaccine in dogs, some still require the vaccine annually. In some respects the subject is complicated, but it’s widely held that overvaccination with the rabies vaccine is associated with harmful side effects in cats and dogs, including vaccine sarcomas at the injection site, autoimmune hemolytic anemia and other autoimmune diseases, seizures and epilepsy.
Evidence suggests that the rabies vaccine has duration of immunity of five to seven years and possibly more, but changing the laws regarding frequency of rabies vaccination is a long and expensive process. The Rabies Challenge Fund was established to cover the cost of a seven-year rabies vaccine challenge study, finance a study of adjuvants used in rabies vaccines, and set up a rabies vaccine adverse-reaction reporting system. The ultimate goal is to extend the legally required interval for rabies booster vaccinations to five and eventually seven years.
Concurrent five- and seven-year rabies challenge studies are beginning their fifth year at the University of Wisconsin School of Veterinary Medicine, conducted by Ronald Schultz, DVM, according to the USDA’s vaccine licensing code. I spoke recently to Dr. Schultz and RCF co-trustee Jean Dodds, DVM, to find out where the research currently stands.
(For anyone who’s unfamiliar with them, Dr. Schultz chairs the pathobiological sciences department at the University of Wisconsin School of Veterinary Medicine and is one of the world’s leading experts on veterinary vaccines. Dr. Dodds is a highly respected veterinary research scientist in the fields of hematology, immunology and endocrinology and founded Hemopet, the first nonprofit national blood bank for animals.)
So what’s the status of the rabies vaccine challenge?
“It’s complicated,” says Dr. Dodds.
The first rabies vaccine studied was selected because of the superior response it provided in USDA challenge trials for licensing, but it’s no longer available due to a company merger. A second licensed rabies vaccine was administered to a separate group of dogs two years after the first study began. That vaccine is the one currently administered to a high percentage of dogs.
Dr. Dodds says both vaccines demonstrated excellent response based on rabies antibody testing for each of the first three study years, but fewer than 30 percent of dogs in the first vaccine group, now six years from vaccination, had serum rabies antibody titer levels considered adequate on the Rapid Fluorescent Focus Inhibition Test (RFFIT). Adequate levels are those above 0.1 IU/mL, which the Centers for Disease Control consider to be an adequate response to rabies vaccination in people.
“Some of the dogs with low or no detected RFFIT antibody were further tested to determine if they had ‘immunologic memory,’” Dr. Dodds says. “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 adequate. The results of this further testing indicated that most of the dogs vaccinated five years ago, even without an adequate RFFIT, do have immunologic memory.”
The conclusion from studies with the initial rabies vaccine is that the immunity conferred by that product was excellent for the first three years but declined during the fourth and fifth years.
“The dogs who completed the five-year study who were given the second rabies vaccine–even those with rabies antibody titers that dropped below the RFFIT adequate level–demonstrated boosted rabies titers,” Dr. Dodds says.
That indicates the presence of an active immune memory. The group of dogs who received the second vaccine four and a half years ago will continue to be studied for two more years.
The next step is to challenge some of the dogs with the rabies virus. That will determine whether the memory response actually protects the dogs.
Doing a rabies challenge is indeed a challenge. It’s expensive and requires special facilities.
“With all of the changes that have occurred in the industry, it’s hard to find a place now to do a rabies challenge,” Dr. Schultz says. “The company that was going to do ours went out of business. There have been a lot of mergers, a lot of changes. You can’t do a rabies challenge just anywhere. There are very, very few places to do it, so that becomes something of a challenge in and of itself. [A rabies challenge is] not something you want to do casually or in any place other than where it can be very well controlled, and the animals have to exist in isolation for a long period of time.”
The results will be submitted for scientific peer review and publication. On the RCF website, Drs. Schultz and Dodds say: “After completion of the peer-review process, it is our hope that this data will establish the world’s first canine rabies titer standard. If this data is further verified by challenge, it will provide a solid scientific base enabling states to incorporate titer clauses into their laws.”