OspA Antibodies Inhibit the In vitro Transmigration of Borreliella burgdorferi

Abstract

Antibodies against Outer surface protein A (OspA) block tick-to-mammal transmission of the Lyme disease spirochete, Borreliella burgdorferi. Evidence suggests that antibodies ingested by a tick during a blood meal entrap OspA-expressing B. burgdorferi within the tick midgut and prevent spirochete migration to the salivary gland and host dermis. In this study, we employed a recently described Transwell system to quantitate the impact of OspA antibodies on B. burgdorferi transmigration. We demonstrate that spirochete movement from the lower Transwell chamber to the upper chamber over a 20-hour period was reduced by >99% in the presence of the transmission-blocking mouse monoclonal IgG antibody (mAb) LA-2. In the case of LA-2, transmigration inhibition coincided with the formation of large antibody-induced bacterial aggregates in the lower Transwell chamber, as determined by dark field microscopy and flow cytometry. Further examination of a panel of human OspA mAbs of varying affinities and epitope specificities revealed that virtually all could block B. burgdorferi transmigration, although most did so in the absence of measurable spirochete agglutination. We propose that transmigration arrest may represent a possible mechanism by which OspA antibodies entrap B. burgdorferi in the tick midgut and limit transmission to mammalian hosts.