Genetic and structural insights into broad neutralization of hepatitis C virus by human V<sub>H</sub>1-69 antibodies.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30613781.
- Also identified by DOI 10.1126/sciadv.aav1882 and PMC identifier 6314831.
- Licence recorded as CC BY-NC.
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Abstract
An effective vaccine to the antigenically diverse hepatitis C virus (HCV) must target conserved immune epitopes. Here, we investigate cross-neutralization of HCV genotypes by broadly neutralizing antibodies (bNAbs) encoded by the relatively abundant human gene family <i>V</i> <i><sub>H</sub></i> <i>1-69</i>. We have deciphered the molecular requirements for cross-neutralization by this unique class of human antibodies from crystal structures of HCV E2 in complex with bNAbs. An unusually high binding affinity is found for germ line-reverted versions of V<sub>H</sub>1-69 precursor antibodies, and neutralization breadth is acquired during affinity maturation. Deep sequencing analysis of an HCV-immune B cell repertoire further demonstrates the importance of the <i>V</i> <sub><i>H</i></sub> <i>1-69</i> gene family in the generation of HCV bNAbs. This study therefore provides critical insights into immune recognition of HCV with important implications for rational vaccine design.
Medical subject headings
- Antibodies, Monoclonal
- Antibodies, Neutralizing
- Dual-Specificity Phosphatases
- Hepacivirus
- Hepatitis C
- Hepatitis C Antibodies