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Publication Abstract from PubMed

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.

Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.,Saunders KO, Nicely NI, Wiehe K, Bonsignori M, Meyerhoff RR, Parks R, Walkowicz WE, Aussedat B, Wu NR, Cai F, Vohra Y, Park PK, Eaton A, Go EP, Sutherland LL, Scearce RM, Barouch DH, Zhang R, Von Holle T, Overman RG, Anasti K, Sanders RW, Moody MA, Kepler TB, Korber B, Desaire H, Santra S, Letvin NL, Nabel GJ, Montefiori DC, Tomaras GD, Liao HX, Alam SM, Danishefsky SJ, Haynes BF Cell Rep. 2017 Feb 28;18(9):2175-2188. doi: 10.1016/j.celrep.2017.02.003. PMID:28249163^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.