Development of an Attenuated Vaccine for the Prevention of Lyme Disease
Abstract
Rationale: Borrelia burgdorferi (Bb) is a corkscrew-shaped bacterium that causes Lyme disease in certain animals, including humans. When it lives within (i.e., infects) its “normal” hosts, such as ticks and rodents, these host animals have evolved such that they tolerate the infection without causing any disease symptoms, as the bacteria appear to be invisible to the immune system of those hosts. Unfortunately other animals, such as humans and dogs, have not evolved in the same way, such that the bacteria are “invisible enough” to those hosts that the immune response cannot clear the infection, but they can still “see” the bacteria enough to cause the immune response to continue to activate. This continual activation to the partially invisible bacteria results in Lyme disease. Because there are now over 400,000 new cases of Lyme disease each year in the U.S., at a cost of $1-$2 billion dollars per year, there is a great need to prevent these rapidly increasing infections. The best approach would be a preventative vaccine, but the only such vaccine was taken off the market almost 20 years ago due to multiple complications; thus, the search for a successful vaccine continues. For many infectious diseases, the best vaccine was to use a “crippled” version of the microbe as a vaccine. The idea behind this is that the crippled (i.e., attenuated) strain could infect the host long enough to show the immune response the most important parts of the microbe that they should recognize to develop a protective and long-lasting immunity, and clear that infection quickly before disease develops. Such attenuated vaccines are still used to prevent many important diseases, such as polio, measles, mumps, rotavirus, typhoid fever, and many others. Subsequently, many such attenuated strains of Bb have been tried as a vaccine, but none were able to protect against Lyme disease. The main problem appears to be that those attenuated strains were cleared by the immune system too quickly (within 1-2 days) before the immune response could “see” the critical parts of the bacteria that they needed to generate an antibody response against to elicit long-lasting protective immunity. Recently, our laboratory has identified a new attenuated mutant that is able to survive for 4-5 days within a host before being cleared by the immune response. When we assessed the immune response to that strain, we noticed that the immune responses were much more strong and complex than those we observe in immune responses to attenuated Bb strains that do not produce long-lasting protective immunity. We then crudely tested the ability of this strain to act as a vaccine by infecting mice with the strain. As noticed previously, this attenuated strain was cleared from the mice within a few days without disease. However, when we tried to re-infect these mice with a large number of highly-infectious Bb, they were completely protected from developing Lyme disease. Thus, for the first time, we have an attenuated mutant that appears to act as an effective vaccine for Lyme disease. Scientific Objective: Based on the successes of our initial studies, we intend to further develop and test this attenuated strain to serve as a Lyme disease vaccine. By changing the way we use this attenuated mutant, including if we can identify the particular Bb molecules that produce the protective immune responses, we should be able to find the optimal conditions to protect from developing Lyme disease (e.g., a Lyme disease vaccine). Aims: Based on these promising findings, our goals can be broken into two phases. In phase (Aim) 1, we will vary the ways that we can use the attenuated strain to get protective immunity, such as change the dose of the immunization, the number of times that we immunize, etc., to find an optimal immunization schedule that provides the best protection. In Aim 2, we will identify the specific parts of Bb that are recognized by the immune response and results in
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110967
Entities
People
- Ronald Wooten
Organizations
- United States Army
- University of Toledo Health Science Campus