Signal peptide substitution improves immunoreactivity of Borrelia burgdorferi protein on E. coli-derived vesicles

Le résumé fourni par la source

Abstract Bacterial infections account for millions of deaths every year, with many lacking preventative options. Bacterial lipoproteins are strong targets for vaccines, but are often expressed in a truncated form that may not properly recapitulate native epitopes, resulting in a reduced, or even ineffective, immune response. Borrelia burgdorferi , the causative agent of Lyme disease, contains numerous surface expressed lipoproteins, including outer surface protein C (OspC). OspC has been explored as a vaccine target in its recombinant form, but has resulted in a wide variation in immune response. This may be due to structural dissimilarity between the recombinant protein and the native protein expressed on the bacterium, as OspC is hypothesized to present itself in the form of a dimer containing non-linear epitopes. Presentation of OspC in a lipid membrane, such as on an outer membrane vesicle (OMV), may improve quaternary epitope presentation across dimers and better mimic the native protein. Here, we explored expression of two proteins on E. coli -derived OMVs: OspC derived from B. burgdorferi sensu lato, and a fusion protein replacing the OspC leader sequence with Braun’s lipoprotein leader sequence (Lpp). Analysis shows that replacing the OspC leader sequence with Lpp improves surface expression and immunoreactivity of the OspC protein on E. coli -derived OMVs exposed to recombinant anti-OspC antibodies derived from B5 and B11, as well as to B. burgdorferi -positive human sera. This strong antibody reactivity indicates that the OMV structure may aid in recapitulating the quaternary epitopes of OspC and provide a strategy for future development of Lyme disease vaccines. Key points • E. coli-derived OMVs expressed OspC when the native leader sequence was replaced with Lpp • Lpp-OspC on OMV surfaces has conserved epitopes that react to B5- and B11-derived antibodies • Lyme-positive serum recognizes Lpp-OspC OMVs with minimal cross-reactivity

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.