期刊
SCIENCE
卷 349, 期 6244, 页码 156-161出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aac5894
关键词
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资金
- IAVI Neutralizing Antibody Consortium and Center
- Collaboration for AIDS Vaccine Discovery funding for the IAVI NAC
- Ragon Institute of MGH, MIT and Harvard
- Helen Hay Whitney Foundation
- National Institute of Allergy and Infectious Diseases [R01-AI073148, P01AI081625]
- CHAVI-ID [1UM1AI100663]
A major goal of HIV-1 vaccine research is the design of immunogens capable of inducing broadly neutralizing antibodies (bnAbs) that bind to the viral envelope glycoprotein (Env). Poor binding of Env to unmutated precursors of bnAbs, including those of the VRC01 class, appears to be a major problem for bnAb induction. We engineered an immunogen that binds to VRC01-class bnAb precursors and immunized knock-in mice expressing germline-reverted VRC01 heavy chains. Induced antibodies showed characteristics of VRC01-class bnAbs, including a short CDRL3 (light-chain complementarity-determining region 3) and mutations that favored binding to near-native HIV-1 gp120 constructs. In contrast, native-like immunogens failed to activate VRC01-class precursors. The results suggest that rational epitope design can prime rare B cell precursors for affinity maturation to desired targets.
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