CTL-mediated immunotherapy can suppress SHIV rebound in ART-free macaques

Jin Fan, Hua Liang, Xiaolin Ji, Shuo Wang, Jing Xue, Dan Li, Hong Peng, Chuan Qin, Cassian Yee () and Yiming Shao ()
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Jin Fan: Peking University Health Science Center
Hua Liang: Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
Xiaolin Ji: Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
Shuo Wang: Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
Jing Xue: Peking Union Medical College
Dan Li: Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
Hong Peng: Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
Chuan Qin: Peking Union Medical College
Cassian Yee: UT MD Anderson Cancer Center
Yiming Shao: Peking University Health Science Center

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: Abstract A major barrier to human immunodeficiency virus (HIV) cure is the existence of viral reservoirs that lead to viral rebound following discontinuation of antiretroviral therapy (ART). We postulate that enhancing cytotoxic T lymphocytes (CTL) targeting conserved envelope (Env) regions can eliminate HIV infected cells in latency. Here, we evaluate the use of adoptively transferred HIV vaccine-induced subtype C Env-specific CTLs in a macaque subtype B simian-human immunodeficiency virus (SHIV) model to determine whether plasma viremia can be controlled after ART interruption. We demonstrate that adoptive cellular therapy (ACT) using autologous Env-specific T cells augmented by therapeutic vaccination can suppress ART-free viral rebound in the SHIV model. Furthermore, phenotypic and functional characterization of adoptively transferred cells in ACT-responsive and nonresponsive animals support a critical role for cross-reactive central memory T cells in viremia control. Our study offers an approach to potentiate immunological suppression of HIV in the absence of antiviral drugs.

Date: 2019
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DOI: 10.1038/s41467-019-09725-6

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