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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Siddappa, NB; Hemashettar, G; Wong, YL; Lakhashe, S; Rasmussen, RA; Watkins, JD; Novembre, FJ; Villinger, F; Else, JG; Montefiori, DC; Ruprecht, RM

Published Date

  • April 2011

Published In

Volume / Issue

  • 40 / 2

Start / End Page

  • 120 - 128

PubMed ID

  • 21044092

Electronic International Standard Serial Number (EISSN)

  • 1600-0684

Digital Object Identifier (DOI)

  • 10.1111/j.1600-0684.2010.00454.x

Language

  • eng

Conference Location

  • Denmark