Protective efficacy of mutant strains of as potential reservoir host-targeted biologics against Lyme disease.

Lyme disease (LD), caused by (), is the most common vector-borne disease in the United States. Methods to control the transmission of to humans via ticks are critical for prevention and elimination of LD. Previously, we showed that deletion of Borrelia hostadaptation Regulator ( mutant) and replacement of 8 conserved residues in Carbon Storage Regulator A of (CsrA, 8S mutant) resulted in upregulation of several lipoproteins due to increased levels of RpoS. Both strains were incapable of colonization in C3H/HeN mice. Clonal isolates lacking linear plasmid 25 derived from strain -B31 or B31-A3 incapable of infection served as control strains. Infection derived mouse serum and serum from Lyme disease patients exhibited reactivity to lysates and purified borrelial lipoproteins (PBLs) from these mutants. Proteomic analysis of PBLs from the mutants revealed similar and unique antigenic components. Two intradermal vaccinations with the live mutant strains induced anti-borrelial antibody responses and reduced load in different tissues compared to unvaccinated C3H/HeN mice following needle challenge with infectious strain B31-A3 strain. The mutant exhibited greater protective efficacy following needle challenge with or infected () nymphs. Transmission of to naïve larvae was reduced from vaccinated mice compared to unvaccinated mice challenged with strain B31-A3. PBLs from mutant strains induced protective immunity in C3H/HeN mice against challenge with infected nymphs. Overall, non-infectious mutant strains can serve as a source of antigens for biologics to interfere with the natural life cycle of .