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.
Funder
Hong Kong Research Grant Council (RGC), Theme-based Research Scheme
Hong Kong Research Grant Council (RGC), French National Research Agency (Agency Nationale de la Recherche)/RGC Joint Research Scheme
Hong Kong Research Grant Council (RGC), General Research Fund
Hong Kong Research Grant Council (RGC), Collaborative Research Fund
Health and Medical Research Fund
University of Hong Kong, University Development Fund
University of Hong Kong, Li Ka Shing Faculty of Medicine Matching Fund
Sanming Project of Medicine in Shenzhen
Publisher
Public Library of Science (PLoS)
Subject
Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology