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Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.
- Source :
-
Cell reports [Cell Rep] 2017 Feb 28; Vol. 18 (9), pp. 2175-2188. - Publication Year :
- 2017
-
Abstract
- Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans-a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors.<br /> (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies, Monoclonal immunology
Binding Sites immunology
HIV Antibodies immunology
HIV Infections immunology
HIV-1 immunology
Macaca mulatta
env Gene Products, Human Immunodeficiency Virus immunology
Antibodies, Neutralizing immunology
Epitopes immunology
Mannose immunology
Polysaccharides immunology
Primates immunology
Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 18
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 28249163
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.02.003