Life After Lyme Disease

New Haven, Conn. — Yale researchers have discovered that a protein found in the saliva of ticks helps protect mice from developing Lyme disease. The findings, published in the November 19th issue of Cell Host & Microbe, may spur the development of a new vaccine against infection from Lyme disease, which is spread through tick bites .

Traditionally, vaccines have directly targeted specific pathogens. This is the first time that antibodies against a protein in the saliva of a pathogen’s transmitting agent (in this case, the tick) have been shown to confer immunity when administered protectively as a vaccine.

The Lyme bacterium known as Borrelia burgdorferi is transmitted by ticks. When it moves through the tick, it is coated with a tick salivary protein known as Salp15. The Yale research team injected Salp15 into healthy mice and found that it significantly protected them from getting Lyme disease. When combined with outer surface proteins of B. burgdorferi , the protection was even greater.

Lead author Erol Fikrig, M.D. of Yale School of Medicine and Howard Hughes Medical Institute said, “The interaction between the Lyme disease agent and ticks is very complex, and the bacteria uses a tick salivary protein to facilitate infection of the mammalian host. By interfering with this important interaction, we can influence infection by the Lyme disease agent.”

Several years ago there was a Lyme vaccine on the market that utilized just the outer surface proteins of the bacteria. It was taken off the market in 2002, and to date no other antigen has been tested in phase III clinical trials.

The authors believe this new strategy of targeting the saliva – the “vector molecule” that a microbe requires to infect a host – may be applicable not just to Lyme disease but to other insect-borne pathogens that cause other human illnesses.

“We believe that it is likely that many arthropod-borne infection agents of medical importance use vector proteins as they move to the mammalian host,” Fikrig explained. “If so, then this paradigm, described with the Lyme disease agent, is likely to be applicable to these illnesses. Currently, we are working to determine if this strategy is likely to be important for West Nile virus infection, dengue fever, and malaria, among other diseases.”

Other researchers were Jianfeng Dai, Penghua Wang, Sarojini Adusumilli, Carmen J. Booth and Sukanya Narasimhan of Yale School of Medicine, and Juan Anguita of the University of Massachusetts. This work was support by grants from the National Institutes of Health.

Contact: Helen Dodson , 203-436-3984

Source: Yale University

Using a powerful microscopic live imaging technique, a research team led by Dr. Justin Radolf, professor in the Departments of Medicine and Genetics and Developmental Biology at the University of Connecticut Health Center, has discovered that how ticks transmit Lyme disease to humans is different than was previously thought. His research is published online in the Journal of Clinical Investigation .

It has been known for some time now that Lyme disease is caused by the transmission of the spirochete bacterium Borrelia burgdorferi from ticks to humans, but the transmission process has been difficult to study for a number of technical reasons.

Dr. Radolf and researchers Star Dunham-Ems and Melissa Caimano tried a novel approach at solving this mystery. They genetically modified a virulent strain of B. burgdorferi with a green fluorescent protein (GFP). “This bacterium glows and can be followed in the living state as it migrates through the tick to the mouse during feeding,” explains Radolf. “Then using a powerful microscopic technique called confocal microscopy, we discovered that the transmission process unfolds quite differently than previously believed.”

Spirochetes in culture are highly motile, and it is widely believed that during feeding, the spirochetes in the mid-gut rapidly move through the wall of the mid-gut. But Radolf and his team discovered that during much of the feeding period, the spirochetes do not move. They actually divide and surround the cells of the mid-gut lining or epithelium, forming tight networks. “We also found that the reason they don’t move is that the tick mid-gut secretes molecules that actually inhibit the motility of the spirochetes,” explains Radolf.

Eventually, spirochetes in the networks reach the base of the epithelium by completely surrounding the epithelial cells. At this point, they become motile, detach, and completely penetrate the mid-gut, although in very small numbers. These bacteria then swim to the salivary glands, which they penetrate en route to the mouse. “So rather than being entirely motility-driven, dissemination of spirochetes within ticks actually happens in two phases,” says Radolf, “which is something we didn’t know before.”

Lyme disease is the most prevalent vector-borne infection in the United States with more than 25,000 new cases reported annually. “The improved understanding of the transmission process revealed by our study could lead to novel strategies for controlling the spread of Lyme disease,” says Radolf.