Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination.
Yik Chun WongWan LiuLok Yan YimXin LiHui WangMing YueMengyue NiuLin ChengLijun LingYanhua DuSamantha M Y ChenKa-Wai CheungHaibo WangXian TangJiansong TangHaoji ZhangYou-Qiang SongLisa A ChakrabartiZhiwei ChenPublished in: PLoS pathogens (2021)
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.
Keyphrases
- antiretroviral therapy
- regulatory t cells
- working memory
- high dose
- dendritic cells
- high glucose
- hiv infected
- human immunodeficiency virus
- diabetic rats
- type iii
- sars cov
- single cell
- hiv positive
- hiv aids
- low dose
- drug induced
- endothelial cells
- lymph node metastasis
- hepatitis c virus
- dna damage
- quality improvement
- risk assessment
- oxidative stress
- stem cell transplantation
- mass spectrometry
- human health
- peripheral blood
- south africa
- atomic force microscopy
- nk cells