Neonatal SHIV infection in rhesus macaques elicited heterologous HIV-1-neutralizing antibodies

Cell Rep. 2023 Mar 28;42(3):112255. doi: 10.1016/j.celrep.2023.112255. Epub 2023 Mar 14.

Abstract

Infants and children infected with human immunodeficiency virus (HIV)-1 have been shown to develop neutralizing antibodies (nAbs) against heterologous HIV-1 strains, characteristic of broadly nAbs (bnAbs). Thus, having a neonatal model for the induction of heterologous HIV-1 nAbs may provide insights into the mechanisms of neonatal bnAb development. Here, we describe a neonatal model for heterologous HIV-1 nAb induction in pathogenic simian-HIV (SHIV)-infected rhesus macaques (RMs). Viral envelope (env) evolution showed mutations at multiple sites, including nAb epitopes. All 13 RMs generated plasma autologous HIV-1 nAbs. However, 8/13 (62%) RMs generated heterologous HIV-1 nAbs with increasing potency over time, albeit with limited breadth, and mapped to multiple nAb epitopes, suggestive of a polyclonal response. Moreover, plasma heterologous HIV-1 nAb development was associated with antigen-specific, lymph-node-derived germinal center activity. We define a neonatal model for heterologous HIV-1 nAb induction that may inform future pediatric HIV-1 vaccines for bnAb induction in infants and children.

Keywords: CP: Immunology; HIV-1 Env glycosylation; HIV-1 env evolution; autologous SHIV NAbs; germinal center activity; neonatal SHIV infection; neonatal heterologous NAbs; neonatal immunity; transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • Child
  • Communicable Diseases*
  • Epitopes
  • HIV Antibodies
  • HIV Infections*
  • HIV-1*
  • Humans
  • Infant
  • Infant, Newborn
  • Macaca mulatta
  • Simian Acquired Immunodeficiency Syndrome*
  • Simian Immunodeficiency Virus*

Substances

  • Broadly Neutralizing Antibodies
  • HIV Antibodies
  • Antibodies, Neutralizing
  • Epitopes