Development of a tier 1 R5 clade C simian–human immunodeficiency virus as a tool to test neutralizing antibody‐based immunoprophylaxis

Abstract

Background While some recently transmitted HIV clade C (HIV‐C) strains exhibited tier 1 neutralization phenotypes, most were tier 2 strains (J Virol 2010; 84:1439). Because induction of neutralizing antibodies (nAbs) through vaccination against tier 2 viruses has proven difficult, we have generated a tier 1, clade C simian–human immunodeficiency virus (SHIV‐C) to permit efficacy testing of candidate AIDS vaccines against tier 1 viruses. Methods SHIV‐1157ipEL was created by swapping env of a late‐stage virus with that of a tier 1, early form. Results After adaptation to rhesus macaques (RM), passaged SHIV‐1157ipEL‐p replicated vigorously in vitro and in vivo while maintaining R5 tropism. The virus was reproducibly transmissible intrarectally. Phylogenetically, SHIV‐1157ipEL‐p Env clustered with HIV‐C sequences. All RM chronically infected with SHIV‐1157ipEL‐p developed high nAb titers against autologous as well as heterologous tier 1 strains. Conclusions SHIV‐1157ipEL‐p was reproducibly transmitted in RM, induced cross‐clade nAbs, and represents a tool to evaluate anti‐HIV‐C nAb responses in primates.