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

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. [Display omitted] •Pathogenic SHIV-infection model of neonate rhesus macaques•Evolution of viral envelope under antibody selection pressure•Induction of polyclonal heterologous tier 2 HIV-1 neutralizing antibodies (nAbs)•Enhanced germinal center activity associated with heterologous HIV nAb induction Hora et al. develop a neonatal rhesus macaque model for induction of polyclonal neutralizing antibodies (nAbs) against heterologous tier 2 HIV-1 strains following pathogenic simian-HIV (SHIV) infection. Understanding the mechanisms of neonatal heterologous HIV-1 nAb induction will provide insights into future pediatric HIV-1 vaccine designs.