Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences |
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| Authors: | Lawrence J. Tartaglia Hui-Wen Chang Benjamin C. Lee Peter Abbink David Ng’ang’a Michael Boyd Christy L. Lavine So-Yon Lim Srisowmya Sanisetty James B. Whitney Michael S. Seaman Morgane Rolland Sodsai Tovanabutra Jintanat Ananworanich Merlin L. Robb Jerome H. Kim Nelson L. Michael Dan H. Barouch |
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| Affiliation: | 1. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.; 2. Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, United States of America.; 3. U.S. Government Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.; 4. International Vaccine Institute, Seoul, Korea.; Emory University, UNITED STATES, |
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| 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. |
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