title: Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences.
abstract: Simian-human immunodeficiency virus (SHIV) challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE) env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection.
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors: Lawrence J
authors: LJ
authors: Tartaglia
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors: Hui-Wen
authors: HW
authors: Chang
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors: Benjamin C
authors: BC
authors: Lee
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors: Peter
authors: P
authors: Abbink
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors: David
authors: D
authors: Ng'ang'a
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors: Michael
authors: M
authors: Boyd
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors: Christy L
authors: CL
authors: Lavine
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors: So-Yon
authors: SY
authors: Lim
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors: Srisowmya
authors: S
authors: Sanisetty
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.|Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America.
authors: James B
authors: JB
authors: Whitney
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.|Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America.
authors: Michael S
authors: MS
authors: Seaman
authors: U.S. Government Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Morgane
authors: M
authors: Rolland
authors: U.S. Government Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Sodsai
authors: S
authors: Tovanabutra
authors: U.S. Government Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Jintanat
authors: J
authors: Ananworanich
authors: U.S. Government Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Merlin L
authors: ML
authors: Robb
authors: U.S. Government Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.|International Vaccine Institute, Seoul, Korea.
authors: Jerome H
authors: JH
authors: Kim
authors: U.S. Government Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Nelson L
authors: NL
authors: Michael
authors: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.|Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America.
authors: Dan H
authors: DH
authors: Barouch
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014766:Viremia / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies