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  • Title: Development of a tier 1 R5 clade C simian-human immunodeficiency virus as a tool to test neutralizing antibody-based immunoprophylaxis.
    Author: Siddappa NB, Hemashettar G, Wong YL, Lakhashe S, Rasmussen RA, Watkins JD, Novembre FJ, Villinger F, Else JG, Montefiori DC, Ruprecht RM.
    Journal: J Med Primatol; 2011 Apr; 40(2):120-8. PubMed ID: 21044092.
    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.
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