New clues about the evolution and ecology of Borellia burgdorferi could point the way to a vaccine for immunizing white-footed mice against the bacteria, according to a study in mBio this week. The study sheds some light on how the immune system of the white-footed mouse responds differently to different strains of the bacterium and could help vaccine developers find ways to immunize the animals against infection. The white-footed mouse is a very common natural reservoir for Lyme-causing bacteria, so a vaccine that keeps these wild mice free of the pathogen could significantly curb the spread of the disease from mice to ticks to humans.
“There’s no human vaccine, and there’s not likely to be one,” says Alan Barbour of the University of California, Irvine, who headed up the study. “We have to focus on lowering the risk. One way to do that is by treating the animals that carry the disease.” Rabies offers a good example of how this might be accomplished, says Barbour. By deploying vaccine-laced food bait, public health officials have managed to lower the rabies infection rate in wildlife and significantly limited the spread of the disease to pets and humans. (I have to admit, that up until he explained this, I imagined that immunizing mice would require tiny little syringes.)
An Expensive Public Health Problem
Although Lyme disease only emerged in the U.S. in the past 40 years or so, around 25,000 cases are now reported every year in this country and the medical costs of these cases are estimated to range in the billions of dollars. Despite the growing importance of the disease, little is known about the evolution and ecology of the bacterium, B. burgdorferi, that causes the illness.
With an eye to eventually designing a Lyme vaccine for wildlife, researchers at UC Irvine sought to understand why as many as 15 different strains of B. burgdorferi exist in the wild at differing degrees of prevalence. In the parts of the country where Lyme disease is most common, the majority of white-footed mice are infected with B. burgdorferi during the course of the year. Unlike humans and lab mice, white-footed mice don’t get sick when they’re infected with B. burgdorferi, so the bacteria grow and multiply within them, and when a deer tick bites it sucks up B. burgdorferi along with its blood meal. Does the white-footed mouse determine which Lyme disease-causing strains are most successful?
B. burgdorferi Strains Elicit Different Immune Reactions
In the lab, the group at UC Irvine exposed white-footed mice to various strains of B. burgdorferi and tracked the course of the infection. All the B. burgdorferi strains infected the white-footed mice, but the strains differed in the extent of infection. Some B. burgdorferi strains managed to grow to high densities in various mouse tissues while others did not.
Barbour says the immune reactions the mice mounted against the various strains explain these discrepancies: the greater the immune response, the fewer bacteria found in a mouse’s tissues and vice-versa. Importantly, the B. burgdorferi strains that grew to greatest densities within the mice are also the strains that are most prevalent in the wild.
When they looked at the immune reaction to individual B. burgdorferi proteins the authors found a complex interplay of reactivities. The mice reacted to a different degree to the various proteins present in a single bacterial strain, which could explain why such a great diversity of B. burgdorferi strains are sustained in the wild, say the authors.
Barbour says knowing more about how the white-footed mouse reacts to all the various B. burgdorferi strains and immunogenic proteins will help vaccine developers like himself select the best proteins to put in a vaccine. “The best candidate for the mouse vaccine is something that’s the same in all the [B. burgdorferi] strains,” says Barbour.
Once a vaccine for the white-footed mouse is developed, it will need to be tested by exposing immunized mice to a selected set of diverse B. burgdorferi strains, says Barbour, and the results of this study can help make that selection. “If we can find five that are representative, that would be an advantage,” Barbour says.
This study, he says, “is going to provide a foundation for future studies in understanding the infection in these animals as we proceed with developing vaccines.”