title: Generation and evaluation of clade C simian-human immunodeficiency virus challenge stocks.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Tartaglia
authors.affiliation: 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.
authors.forename: James B
authors.initials: JB
authors.lastname: Whitney
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: So-Yon
authors.initials: SY
authors.lastname: Lim
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Srisowmya
authors.initials: S
authors.lastname: Sanisetty
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Lavine
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Cecelia
authors.initials: C
authors.lastname: Rademeyer
authors.affiliation: Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA.
authors.forename: Katharine
authors.initials: K
authors.lastname: Ellingson-Strouss
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Stamatatos
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: James
authors.initials: J
authors.lastname: Kublin
authors.affiliation: 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.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification* / Q000472:pathogenicity; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D009092:Mucous Membrane / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification* / Q000472:pathogenicity; D014774:Virulence