Background

Two large pharmaceutical companies have devoted considerable effort to developing a vaccine for Lyme disease, but there are no vaccines for humans available in the United States today.

Double-blind, randomized, placebo-controlled clinical trials—the most rigorous type of clinical trial used today—were completed for each of two Borrelia burgdorferi vaccines manufactured by GlaxoSmithKline (GSK, formerly SmithKline Beecham [SKB]) and Pasteur Merieux Connaught. Each study involved more than 10,000 volunteers from areas of the United States where Lyme disease is common.

Both vaccines were based on a specific part of B. burgdorferi called outer surface protein A (OspA). They were found to be between 49 and 68 percent effective in preventing Lyme disease after two injections, and 76 to 92 percent effective in preventing Lyme disease after three injections. The duration of the protective immunity generated in response to the vaccines is not known. The SKB vaccine was ultimately licensed as LYMErix and approved by the Food and Drug Administration (FDA) in December 1998.

NIAID was not directly involved in the design and implementation of these particular vaccine trials. However, patents for cloning the genes used in making the vaccine, as well as knowledge of how certain antibodies contribute to protective immunity, were derived from basic research grants funded by NIAID.

Soon after licensure, some recipients of LYMErix reported adverse responses, which some believed were attributed to specific segments of the vaccine protein. Subsequent analysis by the FDA and others did not support that conclusion, and the adverse event rate was not shown to be elevated among vaccine recipients. In April 2002, GSK announced that even with the incidence of Lyme disease continuing to rise, sales for LYMErix declined from about 1.5 million doses in 1999 to a projected 10,000 doses in 2002. GSK discontinued manufacturing the vaccine.

In 2018, Valneva reported positive phase I interim results for its Lyme vaccine candidate, which is also an OspA vaccine but includes European Borellia strains and lacks the region of the proteins that some had attributed to adverse events.

NIAID Research

Reservoir-Based Approaches

Infectious disease reservoirs are what scientists call the places or populations that harbor disease-causing pathogens. For example, certain types of wildlife can be long-term carriers, or hosts, of a disease. Rodents are a major reservoir for Lyme disease, so scientists have been looking at ways to prevent them from getting infected with B. burgdorferi. Stopping the bacterial infection in rodents could potentially prevent transmission of the bacteria to the ticks that depend on the rodents in their early life cycle, and, therefore, prevent transmission from ticks to humans.

Several NIAID-funded research groups are investigating the potential of reservoir vaccines to reduce Lyme disease in humans. These oral “bait” vaccines are aimed at preventing mice from becoming infected, thereby interrupting the transmission cycle. Some groups are field testing their products with support from the Centers for Disease Control and Prevention (CDC).

NIAID-funded investigators have developed an experimental bait—and vaccine—delivery system. In a study, mice were given this vaccine-laced bait then exposed to Ixodes ticks carrying multiple strains of B. burgdorferi. Oral vaccination was found to protect 89 percent of the mice from infection and the blood tests showed their immune systems created antibodies to the Lyme bacteria.

NIAID is part of a collaborative effort with researchers at Ventria Bioscience and the Centers for Disease Control and Prevention who are supporting a similar approach. Scientists are working to grow rice plants that contain vaccine elements that could eventually be fed to rodent populations, thus blocking the transmission cycle of the disease from rodents to ticks to people. These findings are consistent with the results reported by other investigators.

In other studies, NIAID grantees have developed a mouse-targeted vaccine using Vaccinia virus. Oral vaccination of mice with a single dose of the vaccine resulted in strong immune system response and full protection from B. burgdorferi infection among vaccinated mice. In addition, scientists observed a significant clearance of B. burgdorferi from infected ticks who fed on vaccinated mice. These findings indicate that such a vaccine may effectively reduce the incidence of Lyme disease in endemic areas.

Human Vaccine Development

NIAID supports significant research efforts focused on human vaccination against Lyme disease. Ongoing research activities include multiple research projects in early-stage discovery and characterization of novel vaccine formulations and targets, including tick saliva-based approaches.

For example, NIAID-supported investigators are characterizing novel vaccine formulations and targets, including approaches that target proteins in tick saliva that are critical for the transmission of the Lyme bacteria to humans. Researchers have identified tick proteins that facilitate transmission of Lyme disease bacteria or that enhance survival of those bacteria in vertebrate hosts. Studies are ongoing to see if vaccines specifically targeting some of these proteins may be used as a strategy or an “anti-tick vaccine” to be used to prevent disease.

Another research team is seeking to modify the successful canine Lyme disease vaccine for use in humans, and is also investigating incorporating antigens against the coinfection anaplasmosis.

In September 2018, NIAID’s advisory Council approved an FY 2020 concept entitled “Targeted Prevention for Tick-Borne Diseases.”  Concepts represent early planning stages for program announcements, requests for applications, or solicitations for Council's input.  Council approval does not guarantee that a concept will become an initiative.