Mechanistic insights into the structure-based design of a CspZ-targeting Lyme disease vaccine.

ABSTRACT: Borrelia burgdorferi (Bb) causes Lyme disease (LD), one of the most common vector-borne diseases in the Northern Hemisphere. Here, we solve the crystal structure of a mutated Bb vaccine antigen, CspZ-YA that lacks the ability to bind to host complement factor H (FH). We generate point mutants of CspZ-YA and identify CspZ-YA_I183Y and CspZ-YA_C187S to trigger more robust bactericidal responses. Compared to CspZ-YA, these CspZ-YA mutants require a lower immunization frequency to protect mice from LD-associated inflammation and bacterial colonization. Antigenicity of wild-type and mutant CspZ-YA proteins are similar, as measured using sera from infected people or immunized female mice. Structural comparison of CspZ-YA with CspZ-YA_I183Y and CspZ-YA_C187S

SUBMITTER: Brangulis K 

PROVIDER: S-EPMC11973211 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature