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

Cell Rep. 2017 Feb 28;18(9):2175-2188. doi: 10.1016/j.celrep.2017.02.003.


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.

Keywords: HIV; V3 glycan; glycan; long-term immunization; vaccination.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology*
  • Binding Sites / immunology
  • Epitopes / immunology*
  • HIV Antibodies / immunology
  • HIV Infections / immunology
  • HIV-1 / immunology
  • Macaca mulatta
  • Mannose / immunology*
  • Polysaccharides / immunology*
  • Primates / immunology*
  • Vaccines / immunology*
  • env Gene Products, Human Immunodeficiency Virus / immunology


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • Polysaccharides
  • Vaccines
  • env Gene Products, Human Immunodeficiency Virus
  • Mannose