Kumaresan, V.; Smith, T.; Lumbreras, M.; MacMackin-Ingle, T.; Kilgore, N.; Starling-Lin, J.; Horn, E. J.; Seshu, J.

Lyme disease (LD), caused by Borrelia burgdorferi (Bb), is the most common vector-borne disease in the United States. Methods to control the transmission of Bb to humans via ticks are critical for prevention and elimination of LD. Previously, we showed that deletion of Borrelia host-adaptation Regulator (badR mutant) and replacement of 8 conserved residues in Carbon Storage Regulator A of Borrelia burgdorferi (CsrABb, 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 Bb-B31 or Bb 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 Bb load in different tissues compared to unvaccinated C3H/HeN mice following needle challenge with infectious Bb strain B31-A3 strain. The badR mutant exhibited greater protective efficacy following needle challenge with Bb or infected Ixodes scapularis (Is) nymphs. Transmission of Bb to naive ls larvae was reduced from vaccinated mice compared to unvaccinated mice challenged with Bb 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 Bb.