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Rapid selection of HIV envelopes that bind to neutralizing antibody B cell lineage members with functional improbable mutations.
- Source :
-
Cell reports [Cell Rep] 2021 Aug 17; Vol. 36 (7), pp. 109561. - Publication Year :
- 2021
-
Abstract
- Elicitation of broadly neutralizing antibodies (bnAbs) by an HIV vaccine will involve priming the immune system to activate antibody precursors, followed by boosting immunizations to select for antibodies with functional features required for neutralization breadth. The higher the number of acquired mutations necessary for function, the more convoluted are the antibody developmental pathways. HIV bnAbs acquire a large number of somatic mutations, but not all mutations are functionally important. In this study, we identify a minimal subset of mutations sufficient for the function of the naturally occurring V3-glycan bnAb DH270.6. Using antibody library screening, candidate envelope immunogens that interact with DH270.6-like antibodies containing this set of key mutations are identified and selected in vitro. Our results demonstrate that less complex B cell evolutionary pathways than those naturally observed exist for the induction of HIV bnAbs by vaccination, and they establish rational approaches to identify boosting candidate immunogens.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Cell Line
Humans
Mutagenesis genetics
Protein Binding
Vaccination
env Gene Products, Human Immunodeficiency Virus chemistry
Antibodies, Neutralizing immunology
B-Lymphocytes cytology
Cell Lineage
Mutation genetics
env Gene Products, Human Immunodeficiency Virus genetics
env Gene Products, Human Immunodeficiency Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 36
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 34407396
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.109561