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Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates

Authors :
Kevin O. Saunders
Nathan I. Nicely
Kevin Wiehe
Mattia Bonsignori
R. Ryan Meyerhoff
Robert Parks
William E. Walkowicz
Baptiste Aussedat
Nelson R. Wu
Fangping Cai
Yusuf Vohra
Peter K. Park
Amanda Eaton
Eden P. Go
Laura L. Sutherland
Richard M. Scearce
Dan H. Barouch
Ruijun Zhang
Tarra Von Holle
R. Glenn Overman
Kara Anasti
Rogier W. Sanders
M. Anthony Moody
Thomas B. Kepler
Bette Korber
Heather Desaire
Sampa Santra
Norman L. Letvin
Gary J. Nabel
David C. Montefiori
Georgia D. Tomaras
Hua-Xin Liao
S. Munir Alam
Samuel J. Danishefsky
Barton F. Haynes
Source :
Cell Reports, Vol 18, Iss 9, Pp 2175-2188 (2017)
Publication Year :
2017
Publisher :
Elsevier, 2017.

Abstract

Summary: 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. : Most bnAb epitopes on HIV-1 Envelope include host glycans, but previous Env vaccines have not induced glycan-dependent antibodies. Saunders et al. describe here the ontogeny, crystal structure with glycan, and virion Man9GlcNAc2-dependent neutralization for glycan-reactive antibodies induced by envelope vaccination. Keywords: HIV, V3 glycan, vaccination, glycan, long-term immunization

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
22111247
Volume :
18
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.f020d40e9877461f93e8d9d15c7fa9e4
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2017.02.003