Natural tick challenge crucial for |
Vaccines for canine Lyme disease should be tested with a natural challenge to assure that dogs will be protected against the same conditions they encounter in nature, researchers say.
Canine Lyme borreliosis is caused by the spirochete Borrelia burgdorferi, which is transmitted by the Ixodes tick species. For many years, Lyme has been widely recognized as the most common arthropod-transmitted disease in the United States. Only recently, however, have researchers come to realize that the tick itself plays an important role in transmission of the disease.
“The salivary glands of ticks secrete a complex solution, including a substance that suppresses the immune response of the host,” says Ulrike Munderloh, DVM, PhD, research associate at the University of Minnesota’s Department of Entomology. “The substance acts on white blood cells to disable them and knock out the defense response.”
Surface proteins differ
Munderloh and others also have found differences between naturally transmitted and lab-grown B. burgdorferi. Specifically, the surface proteins of B. burgdorferi spirochetes transmitted by ticks are different from those of culture-grown spirochetes, Munderloh says. Surface proteins are primarily responsible for inducing an antibody response in the host.
Munderloh says the findings demonstrate that it is “very important” to use a natural tick challenge for evaluating vaccines designed to prevent Lyme borreliosis in dogs.
“It is the only way to be sure that a vaccine protects against the same conditions dogs encounter in the field,” she says.
This research was a key reason that Solvay Animal Health, Inc., Mendota Heights, Minn., used a natural tick challenge when it developed Galaxy Lyme, a killed, bivalent vaccine for canine Lyme borreliosis.
Mimicked field conditions
Jon Korshus, associate scientist with the company, says, “We wanted to confirm the efficacy of the product under field-like conditions. By using a natural tick challenge, we mimicked exactly the route of transmission that occurs in the field.”
In fact, Korshus, with the help of colleagues, collected ticks in Lyme-endemic areas to test the vaccine. The presence of B. burgdorferi in the ticks used in challenge studies was confirmed.
In its primary study, the company vaccinated 20 dogs with Galaxy Lyme and designated another 15 non-vaccinated dogs as controls. After seven months—a period that covers the tick season in most areas endemic for Lyme borreliosis—all 35 dogs were challenged with infected ticks.
Because it generally takes from two to five months after tick exposure for dogs to develop clinical signs of Lyme borreliosis, the dogs were observed for the next nine months. “We found that some dogs can develop clinical signs as soon as one month after tick attachment,” Korshus says. “It is important to observe dogs daily for longer than five months following tick challenge.”
Assessed by its ability to reduce the incidence of lameness—the primary clinical sign of Lyme borreliosis—the vaccine was found to be 88% effective. Based on spirochete recovery, the vaccine was 95% effective in preventing B. burgdorferi infection. Spirochetes were recovered from every control dog with lameness, but from only one vaccinated dog, Korshus says.
“To our knowledge, this is the only Lyme vaccine on the market that has been tested with a controlled, natural tick challenge,” the scientist adds. “The other choice would have been to challenge vaccinated dogs by inoculating them with culture-grown spirochetes, which are not the same or as virulent as spirochetes transmitted by the tick and lack the tick secretions that suppress immune response.”
Safety studies
Solvay Animal Health, Inc., also conducted “exaggerated” safety studies, says Mark Mellencamp, Ph.D., a scientist with the company. Three groups of 20 dogs each received a different combination of multiple vaccinations and challenge with B. burgdorferi. They were observed for over 270 days (nine months), and there was no evidence of immunopathology, says Mellencamp, who is in charge of canine vaccine development for the company.
Galaxy Lyme was further tested in 13 veterinary practices in states endemic for Lyme. Of 2,090 intramuscular doses administered by practitioners, nearly 97% were considered reaction-free, Mellencamp says.
The new bivalent Lyme borreliosis vaccine should provide broader and better coverage than a monovalent vaccine, says a university investigator.
Ronald F. Schell, PhD, professor of medical microbiology and immunology at the University of Wisconsin Medical School, Madison, says that most Lyme borreliosis spirochetes in North America can be categorized under one seroprotective group.
He and his associates, however, have documented another isolate, called C-1-11, which represents a separate seroprotective group. “But we do not know how prevalent it is,” Schell says.
In experiments, it was demonstrated that antibodies generated by isolates in each seroprotective group would kill isolates from the same group, but not isolates in the other seroprotective groups.
In other words, to kill Lyme borreliosis C-1-11 isolates, a vaccine must contain isolates from that seroprotective group, Schell says.
“Our research also shows that combining isolates from both seroprotective groups enhances the antibody response,” he says.
Based on this research, Schell has concluded that a bivalent vaccine for Lyme borreliosis is better than a monovalent vaccine, even in areas where C-1-11 has not been found.
Galaxy Lyme is the only Lyme borreliosis vaccine on the market that contains isolates from both seroprotective groups, according to Solvay Animal Health, Inc.