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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, 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 :
- Biology (General)
QH301-705.5
Subjects
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