Identification of a HIV Gp41-Specific Human Monoclonal Antibody With Potent Antibody-Dependent Cellular Cytotoxicity

Front Immunol. 2018 Nov 16:9:2613. doi: 10.3389/fimmu.2018.02613. eCollection 2018.

Abstract

Antibody-Dependent Cellular Cytotoxicity (ADCC) is a major mechanism of protection against viral infections in vivo. Identification of HIV-1-specific monoclonal antibodies (mAbs) with potent ADCC activity may help develop an effective HIV-1 vaccine. In present study, we isolated such human mAb, designated E10, from an HIV-1-infected patient sample by single B cell sorting and single cell PCR. E10 bound to gp140 trimer and linear peptides derived from gp41 membrane proximal external region (MPER). E10 epitope (QEKNEQELLEL) overlapped with mAb 2F5 epitope. However, E10 differentiated from 2F5 in neutralization breadth and potency, as well as ADCC activity. E10 showed low neutralization activity and narrow spectrum of neutralization compared to 2F5, but it mediated higher ADCC activity than 2F5 at low antibody concentration. Fine mapping of E10 epitope may potentiate MPER-based subunit vaccine development.

Keywords: ADCC; HIV; MPER; antibody; epitope; gp41.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / metabolism*
  • Antibody-Dependent Cell Cytotoxicity
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / immunology
  • Flow Cytometry
  • HIV Antibodies / isolation & purification
  • HIV Antibodies / metabolism*
  • HIV Envelope Protein gp41 / genetics
  • HIV Envelope Protein gp41 / immunology
  • HIV Infections / immunology*
  • HIV-1 / physiology*
  • Humans
  • Immunity, Humoral
  • Peptides / genetics
  • Peptides / immunology
  • Single-Cell Analysis

Substances

  • AIDS Vaccines
  • Antibodies, Monoclonal
  • Epitopes, B-Lymphocyte
  • HIV Antibodies
  • HIV Envelope Protein gp41
  • Peptides