Identification of immunoprotective antigens for preventing lyme disease - borrelia burgdorferi (BB) is the causative agent of lyme disease, which is the leading vector-borne disease in north america

The National Institute of Allergy and Infectious Diseases awarded the University of Toledo $768,796 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to identify immunoprotective antigens for preventing Lyme disease caused by Borrelia burgdorferi. The research will evaluate attenuated bacterial mutants as vaccine candidates, building on the recipient's prior identification of a BB strain lacking a chemotaxis-related gene that is rapidly cleared from infected hosts without causing clinical disease while generating protective B and T cell responses. The award funds a five-year project through August 31, 2031, with place of performance at the University of Toledo Health Science Campus in Toledo, Ohio. This is a Project Grant, classified as assistance funding.

If not diagnosed and treated appropriately with antibiotics, BB can produce lasting and debilitating disease in multiple tissues, resulting in significant personal and public health costs. Due to its rapid increase world-wide throughout the northern hemisphere, there is great interest in developing preventative vaccines against lyme disease. Although there have been many attempts to develop such a vaccine, only a single ospa vaccine has been approved by the FDA for public use. However, this vaccine has been pulled from public offering, leaving no commercially-available lyme disease vaccine. For many pathogenic microbes, the use of mutant strains that are attenuated for virulence have proved to be highly effective for generating protective immunity. This is because those strains can survive within a host long- enough to express virulence proteins that are critical for host survival, but not long enough to cause clinical disease. However, this attenuated infection does allow generation of b and t cells that are subsequently protective against challenge with fully virulent strains of that pathogen. There have been several attempts to use attenuated mutants as vaccines against BB, but they have either elicited poor levels of antibodies or were unable to confer effective protection. One reason for these failures is that these mutants are cleared very quickly from the host and thus do not elicit an effective immune response against virulence proteins that are only upregulated in the vertebrate host. Recently, our group has identified a BB strain that lacks a single chemotaxis-related gene that dramatically affects its motility patterns in vitro and in vivo. When tested in mice, this mutant was cleared from the host within 4 days and without developing lyme disease, but the infection was sufficiently long to elicit significant levels of BB-specific antibodies, a substantial number of which were against antigens that are only expressed within a vertebrate host. Importantly, immunization of mice with this attenuated strain was able to protect 100% of the mice needle- challenged with 10X the ID50 from this BB strain. Thus, this attenuated strain appears capable of generating antibodies able to prevent lyme disease. Based on these promising findings, our goals are to: aim 1. Optimize and test the ability of the attenuated vaccine to confer protective immunity against lyme disease. Aim 2. Use protective VS non-protective antisera identified/generated in aim 1 to screen a BB whole-proteome array to identify those proteins that correlate with protective immunity. These best candidates will be tested for their abilities to elicit protective immunity and potential to serve as a recombinant therapeutic against lyme disease.