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

Authors :
Francois Villinger
David C. Montefiori
Francis J. Novembre
James G. Else
Jennifer D. Watkins
Samir K. Lakhashe
Girish Hemashettar
Ruth M. Ruprecht
Yin Ling Wong
Robert A. Rasmussen
Nagadenahalli B. Siddappa
Source :
Journal of Medical Primatology. 40:120-128
Publication Year :
2010
Publisher :
Wiley, 2010.

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.

Details

ISSN :
00472565
Volume :
40
Database :
OpenAIRE
Journal :
Journal of Medical Primatology
Accession number :
edsair.doi...........be042a873f2154057415a70ea3559648
Full Text :
https://doi.org/10.1111/j.1600-0684.2010.00454.x