Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination

Yik Chun Wong; Wan Liu; Lok Yan Yim; Xin Li; Hui Wang; Ming Yue; Mengyue Niu; Lin Cheng; Lijun Ling; Yanhua Du; Samantha M Y Chen; Ka-Wai Cheung; Haibo Wang; Xian Tang; Jiansong Tang; Haoji Zhang; Youqiang Song; Lisa A Chakrabarti; Zhiwei Chen

doi:10.1371/journal.ppat.1009647

Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination

PLoS Pathog. 2021 Jun 14;17(6):e1009647. doi: 10.1371/journal.ppat.1009647. eCollection 2021 Jun.

Authors

Yik Chun Wong^{1

2}, Wan Liu¹, Lok Yan Yim^{1

2}, Xin Li^{1

3}, Hui Wang², Ming Yue⁴, Mengyue Niu¹, Lin Cheng², Lijun Ling¹, Yanhua Du¹, Samantha M Y Chen¹, Ka-Wai Cheung¹, Haibo Wang¹, Xian Tang^{2

5}, Jiansong Tang¹, Haoji Zhang³, Youqiang Song⁴, Lisa A Chakrabarti⁵, Zhiwei Chen^{1

2}

Affiliations

¹ AIDS Institute, Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
² HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Shenzhen, China.
³ Department of Veterinary Medicine, Foshan University, Foshan, China.
⁴ School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
⁵ Virus and Immunity Unit, Pasteur Institute, Paris, France; INSERM U1108, Paris, France.

Abstract

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 SHIVSF162P3CN. 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes / immunology*
Female
Immunologic Memory / immunology*
Macaca mulatta
Mice
Mice, Inbred C57BL
Programmed Cell Death 1 Receptor / immunology*
SAIDS Vaccines / immunology*
Simian Acquired Immunodeficiency Syndrome / immunology
Simian Acquired Immunodeficiency Syndrome / prevention & control
Simian Immunodeficiency Virus
Vaccines, DNA / immunology
Viremia / prevention & control*
gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

Programmed Cell Death 1 Receptor
SAIDS Vaccines
Vaccines, DNA
gag Gene Products, Human Immunodeficiency Virus

Grants and funding

This work was supported by the Hong Kong Research Grant Council (RGC) via Theme-based Research Scheme (T11-706/18-N), The French National Research Agency (Agency Nationale de la Recherche)/RGC Joint Research Scheme (A-HKU709/14), General Research Fund (762712) and Collaborative Research Fund (HKU5/CRF/13G). This work was also supported by Health and Medical Research Fund (17160762) from Food and Health Bureau, The Government of Hong Kong Special Administration Region of the People?s Republic of China, University Development Fund (http://www.rss.hku.hk/news/page/2) from The University of Hong Kong, Li Ka Shing Faculty of Medicine Matching Fund (http://www.rss.hku.hk/news/page/2) from The University of Hong Kong, Mega-Projects of National Science Research for the 13^th Five-Year Plan in China (2018ZX10731101-002-001) and the Sanming Project of Medicine in Shenzhen (AR160087). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.