Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors
Abstract
Hepatitis C virus (HCV) infects 1-2% of the world's population, but a vaccine to limit spreading of this silent killer is unavailable. A leading strategy in vaccine design to counter the genetic variability of HCV is to elicit broadly neutralizing antibodies (bnAbs) targeting conserved viral epitopes. The HCV antigenic site 412-423 (AS412) is highly conserved and a prime vaccine target. In this study, the genetic and structural properties of murine bnAbs targeting AS412 were determined. Using specific molecular interactions encoded in the antibody germline genes and those acquired by somatic hypermutation, two distinct antibody lineages recognize AS412 in near identical conformations. The results provide key insights in the development of HCV bnAbs for rational vaccine design.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- July 2018
- DOI:
- 10.1073/pnas.1802378115
- Bibcode:
- 2018PNAS..115.7569A