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

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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… Click to show full 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.Viral rebound following discontinuation of antiretroviral therapy (ART) is a major obstacle for HIV cure. Here, the authors show that adoptive cellular therapy using autologous Env-specific T cells augmented by therapeutic vaccination can control viral rebound after ART interruption in a SHIV macaque model.

Keywords: viral rebound; rebound art; art free; shiv; therapy

Journal Title: Nature Communications
Year Published: 2019

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