A new lease on life for an HIV-neutralizing antibody class and vaccine target.
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ABSTRACT:
SUBMITTER: Burton DR
PROVIDER: S-EPMC7896332 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
A new lease on life for an HIV-neutralizing antibody class and vaccine target.
Proceedings of the National Academy of Sciences of the United States of America 20210201 7
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Project description:Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to human immunodeficiency virus (HIV) and other pathogens.
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Project description:Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.
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