HIV-1 Consensus Envelope-Induced Broadly Binding Antibodies

AIDS Res Hum Retroviruses. 2017 Aug;33(8):859-868. doi: 10.1089/AID.2016.0294. Epub 2017 May 30.

Abstract

Antibodies that cross-react with multiple HIV-1 envelopes (Envs) are useful reagents for characterizing Env proteins and for soluble Env capture and purification assays. We previously reported 10 murine monoclonal antibodies induced by group M consensus Env, CON-6 immunization. Each demonstrated broad cross-reactivity to recombinant Envs. Here we characterized the Env epitopes to which they bind. Seven mapped to linear epitopes in gp120, five at the Env N-terminus, and two at the Env C-terminus. One antibody, 13D7, bound at the gp120 N-terminus (aa 30-42), reacted with HIV-1-infected CD4+ T cells, and when expressed in a human IgG1 backbone, mediated antibody-dependent cellular cytotoxicity. Antibody 18F11 bound at the gp120 C-terminus (aa 445-459) and reactivity was glycan dependent. Antibodies 13D7, 3B3, and 16H3 bound to 100 percent of HIV-1 Envs tested in ELISA and sodium dodecyl sulfate/polyacrylamide gel electrophoresis/western blot analysis. These data define the epitopes of monoclonal antibody reagents for characterization of recombinant Envs, one epitope of which is also expressed on the surface of HIV-1-infected CD4+ T cells.

Keywords: ADCC; HIV; antibody-mediated immunity; monoclonal; vaccine design.

Publication types

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

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / isolation & purification
  • Antibody-Dependent Cell Cytotoxicity
  • Consensus Sequence*
  • Epitope Mapping
  • Epitopes / genetics
  • Epitopes / immunology*
  • HIV Antibodies / immunology*
  • HIV Antibodies / isolation & purification
  • HIV-1 / immunology*
  • Mice, Inbred BALB C
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • AIDS Vaccines
  • Antibodies, Monoclonal
  • Epitopes
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus