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

HIV-1 infected infants and children have been shown to develop neutralizing antibodies (NAbs) against heterologous HIV-1 strains, characteristic of broadly-NAbs (bnAbs). Thus, having a neonatal model for induction of heterologous HIV-1 NAbs may provide insights into the mechanisms of neonatal bnAb-development. Here, we established a neonatal model for heterologous HIV-1 NAb induction in pathogenic Simian-HIV (SHIV)-infected rhesus macaques (RMs). Viral envelope (env) evolution revealed 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 overtime, 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.