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J Virol. 2015 Feb;89(4):1965-74. doi: 10.1128/JVI.03279-14. Epub 2014 Dec 3.

Generation and evaluation of clade C simian-human immunodeficiency virus challenge stocks.

Author information

1
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA.
2
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
3
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
4
Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
5
Seattle Biomedical Research Institute, Seattle, Washington, USA.
6
Seattle Biomedical Research Institute, Seattle, Washington, USA Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
7
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
8
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA dbarouch@bidmc.harvard.edu.

Abstract

The development of a panel of mucosally transmissible simian-human immunodeficiency virus (SHIV) challenge stocks from multiple virus clades would facilitate preclinical evaluation of candidate HIV-1 vaccines and therapeutics. The majority of SHIV stocks that have been generated to date have been derived from clade B HIV-1 env sequences from viruses isolated during chronic infection and typically required serial animal-to-animal adaptation for establishing mucosal transmissibility and pathogenicity. To capture essential features of mucosal transmission of clade C viruses, we produced a series of SHIVs with early clade C HIV-1 env sequences from acutely HIV-1-infected individuals from South Africa. SHIV-327c and SHIV-327cRM expressed env sequences that were 99.7 to 100% identical to the original HIV-1 isolate and did not require in vivo passaging for mucosal infectivity. These challenge stocks infected rhesus monkeys efficiently by both intrarectal and intravaginal routes, replicated to high levels during acute infection, and established chronic setpoint viremia in 13 of 17 (76%) infected animals. The SHIV-327cRM challenge stock was also titrated for both single, high-dose intrarectal challenges and repetitive, low-dose intrarectal challenges in rhesus monkeys. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines and other interventions aimed at preventing clade C HIV-1 infection.

IMPORTANCE:

We describe the development of two related clade C SHIV challenge stocks. These challenge stocks should prove useful for preclinical testing of vaccines and other interventions aimed at preventing clade C HIV-1 infection.

PMID:
25473043
PMCID:
PMC4338880
DOI:
10.1128/JVI.03279-14
[Indexed for MEDLINE]
Free PMC Article

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