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

Autor: Wong YC; 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.; 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., Liu W; 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., Yim LY; 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.; 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., Li X; 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.; Department of Veterinary Medicine, Foshan University, Foshan, China., Wang H; 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., Yue M; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China., Niu M; 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., Cheng L; 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., Ling L; 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., Du Y; 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., Chen SMY; 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., Cheung KW; 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., Wang H; 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., Tang X; 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.; Virus and Immunity Unit, Pasteur Institute, Paris, France; INSERM U1108, Paris, France., Tang J; 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., Zhang H; Department of Veterinary Medicine, Foshan University, Foshan, China., Song Y; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China., Chakrabarti LA; Virus and Immunity Unit, Pasteur Institute, Paris, France; INSERM U1108, Paris, France., Chen Z; 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.; 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.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2021 Jun 14; Vol. 17 (6), pp. e1009647. Date of Electronic Publication: 2021 Jun 14 (Print Publication: 2021).
DOI: 10.1371/journal.ppat.1009647
Abstrakt: 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.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Z.C. is a co-inventor on the PD1-based vaccine patent. However, ZC and all other authors do not have any competing interests or additional financial interests.
Databáze: MEDLINE
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