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Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination
Author(s) -
Yik Chun Wong,
Liu Wan,
Lok Yan Yim,
Xin Li,
Hui Wang,
Yue Ming,
Mang Niu,
Lin Cheng,
Liuyi Ling,
Yanhua Du,
Samantha M. Y. Chen,
Kmc Cheung,
Haibo Wang,
Xian Tang,
Jiansong Tang,
Haoji Zhang,
YouQiang Song,
Lisa A. Chakrabarti,
Zhiwei Chen
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009647
Subject(s) - viremia , immunology , effector , vaccination , virology , cd8 , simian immunodeficiency virus , cytotoxic t cell , memory t cell , biology , antigen , virus , biochemistry , in vitro
HIV-1 functional cure requires sustained viral suppression without antiretroviral therapy. While effector-memory CD8 + T lymphocytes are essential for viremia control, few vaccines elicit such cellular immunity that could be potently recalled upon viral infection. Here, we investigated a program death-1 (PD1)-based vaccine by fusion of simian immunodeficiency virus capsid antigen to soluble PD1. Homologous vaccinations suppressed setpoint viremia to undetectable levels in vaccinated macaques following a high-dose intravenous challenge by the pathogenic SHIV SF162P3CN . Poly-functional effector-memory CD8 + T cells were not only induced after vaccination, but were also recalled upon viral challenge for viremia control as determined by CD8 depletion. Vaccine-induced effector memory CD8 + subsets displayed high cytotoxicity-related genes by single-cell analysis. Vaccinees with sustained viremia suppression for over two years responded to boost vaccination without viral rebound. These results demonstrated that PD1-based vaccine-induced effector-memory CD8 + T cells were recalled by AIDS virus infection, providing a potential immunotherapy for functional cure.

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