| Autor: |
Wong, Yik Chun, Liu, Wan, Yim, Lok Yan, Li, Xin, Wang, Hui, Yue, Ming, Niu, Mengyue, Cheng, Lin, Ling, Lijun, Du, Yanhua, Chen, Samantha M. Y., Cheung, Ka-Wai, Wang, Haibo, Tang, Xian, Tang, Jiansong, Zhang, Haoji, Song, Youqiang, Chakrabarti, Lisa A., Chen, Zhiwei |
| Předmět: |
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| Zdroj: |
PLoS Pathogens; 6/14/2021, Vol. 17 Issue 6, p1-25, 25p |
| 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. Author summary: HIV-1/AIDS remains a major global pandemic although treatment regimen has improved. Identifying efficacious vaccines and therapeutics to achieve long-term viral control with very low/undetectable plasma viral loads in the absence of antiretroviral therapy, a status known as functional cure, would be highly beneficial. We previously demonstrated that antigens fused to a soluble program death-1 (PD1) domain could effectively bind and be cross-presented by dendritic cells that constitutively expressed PD1 ligands. When applied in the form of DNA vaccination, this antigen-targeting strategy was highly immunogenic in mice. Here, we investigated the efficacy of the PD1-based DNA vaccine approach against pathogenic simian-human immunodeficiency virus challenge in rhesus monkeys. Our results showed that homologous PD1-based DNA vaccinations induced highly functional effector-memory CD8+ T cells carrying a unique cytotoxicity gene expression profile. These T cells actively supressed viremia in monkeys and were re-activated via boost vaccination at 2 years after viral challenge without viral rebound. In summary, our study demonstrates the potential application of PD1-based DNA vaccination to control AIDS virus infection. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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