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Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates
Saunders, Kevin O. ; Nicely, Nathan ; Wiehe, Kevin ; Bonsignori, Mattia ; Meyerhoff, R. Ryan ; Parks, Robert ; Walkowicz, William E. ; Aussedat, Baptiste ; Wu, Nelson R. ; Cai, Fangping ... show 10 more
Saunders, Kevin O.
Nicely, Nathan
Wiehe, Kevin
Bonsignori, Mattia
Meyerhoff, R. Ryan
Parks, Robert
Walkowicz, William E.
Aussedat, Baptiste
Wu, Nelson R.
Cai, Fangping
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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.
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2017-02-28
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Elsevier
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Saunders, K., Nicely, N. I., Wiehe, K., (2017), Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates, Cell Reports, https://doi.org/10.1073/pnas.1615660114