Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors
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- Fernando Aleman
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037;
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- Netanel Tzarum
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037;
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- Leopold Kong
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037;
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- Kenna Nagy
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037;
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- Jiang Zhu
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037;
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- Ian A. Wilson
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037;
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- Mansun Law
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037;
説明
<jats:title>Significance</jats:title> <jats:p>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.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 115 (29), 7569-7574, 2018-06-28
Proceedings of the National Academy of Sciences