CspZ FH-binding sites as epitopes promote antibody-mediated Lyme borreliae clearance

Abstract

Transmitted by ticks, the bacterium Borrelia burgdorferi sensu lato (Bbsl) is the causative agent of Lyme disease (LD), the most common vector-borne disease in the Northern hemisphere. No effective vaccines are currently available. Bbsl produces the CspZ protein that binds to the complement inhibitor, Factor H (FH), promoting evasion of the host complement system. We previously showed that while vaccination with CspZ did not protect mice from Bb infection, mice can be protected after immunization with CspZ-Y207A/Y211A (CspZ-YA), a CspZ mutant protein without FH-binding activity. To further study the mechanism of this protection, herein we evaluated both poly-and monoclonal antibodies recognizing CspZ FH-binding or non-FH-binding sites. We found that the anti-CspZ antibodies that recognize the FH-binding sites (i.e., block FH-binding activity) more efficiently eliminate Bbsl in vitro than those that bind to the non-FH-binding sites, and passive inoculation with anti-FH binding site antibodies eradicated Bbsl in vivo. Antibodies against non-FH-binding sites did not have the same effect. These results emphasize the importance of CspZ FH-binding sites in triggering a protective antibody response against Bbsl in future LD vaccines.