[PDF][PDF] Vaccine elicitation of high mannose-dependent neutralizing antibodies against the V3-glycan broadly neutralizing epitope in nonhuman primates

KO Saunders, NI Nicely, K Wiehe, M Bonsignori… - Cell reports, 2017 - cell.com
KO Saunders, NI Nicely, K Wiehe, M Bonsignori, RR Meyerhoff, R Parks, WE Walkowicz
Cell reports, 2017cell.com
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 …
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.
cell.com