Structural highlights
Publication Abstract from PubMed
Elicitation of broadly neutralizing antibodies (bnAbs) is a leading strategy in rational vaccine design against antigenically diverse pathogens. Here, we studied a panel of monoclonal antibodies (mAbs) from mice immunized with the hepatitis C virus (HCV) envelope glycoproteins E1E2. Six of the mAbs recognize the conserved E2 antigenic site 412-423 (AS412) and cross-neutralize diverse HCV genotypes. Immunogenetic and structural analysis revealed that the antibodies originated from two different germline (GL) precursors and bind AS412 in a beta-hairpin conformation. Intriguingly, the anti-HCV activity of one antibody lineage is associated with maturation of the light chain (LC), whereas the other lineage is dependent on heavy-chain (HC) maturation. Crystal structures of GL precursors of the LC-dependent lineage in complex with AS412 offer critical insights into the maturation process of bnAbs to HCV, providing a scientific foundation for utilizing the mouse model to study AS412-targeting vaccine candidates.
Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors.,Aleman F, Tzarum N, Kong L, Nagy K, Zhu J, Wilson IA, Law M Proc Natl Acad Sci U S A. 2018 Jun 28. pii: 1802378115. doi:, 10.1073/pnas.1802378115. PMID:29954862[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Aleman F, Tzarum N, Kong L, Nagy K, Zhu J, Wilson IA, Law M. Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors. Proc Natl Acad Sci U S A. 2018 Jun 28. pii: 1802378115. doi:, 10.1073/pnas.1802378115. PMID:29954862 doi:http://dx.doi.org/10.1073/pnas.1802378115
