HIV-1 neutralizing antibodies provide sterilizing immunity by blocking infection of the first cells

Cell Rep Med. 2023 Oct 17;4(10):101201. doi: 10.1016/j.xcrm.2023.101201. Epub 2023 Oct 6.

Abstract

Neutralizing antibodies targeting HIV-1 Env have been shown to protect from systemic infection. To explore whether these antibodies can inhibit infection of the first cells, challenge viruses based on simian immunodeficiency virus (SIV) were developed that use HIV-1 Env for entry into target cells during the first replication cycle, but then switch to SIV Env usage. Antibodies binding to Env of HIV-1, but not SIV, block HIV-1 Env-mediated infection events after rectal exposure of non-human primates to the switching challenge virus. After natural exposure to HIV-1, such a reduction of the number of first infection events should be sufficient to provide sterilizing immunity in the strictest sense in most of the exposed individuals. Since blocking infection of the first cells avoids the formation of latently infected cells and reduces the risk of emergence of antibody-resistant mutants, it may be the best mode of protection.

Keywords: AIDS; Fc-effector function; HIV; mucosal immunity; neutralizing antibody; sterilizing immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • HIV Antibodies
  • HIV Infections*
  • HIV-1*
  • Macaca mulatta
  • Simian Acquired Immunodeficiency Syndrome* / prevention & control
  • Simian Immunodeficiency Virus*

Substances

  • Antibodies, Viral
  • Antibodies, Neutralizing
  • HIV Antibodies