Therapeutic vaccine-mediated Gag-specific CD8+ T-cell induction under anti-retroviral therapy augments anti-virus efficacy of CD8+ cells in simian immunodeficiency virus-infected macaques
| Autor: | Tomoyuki Miura, Saori Matsuoka, Midori Nakamura-Hoshi, Tetsuro Matano, Tsuyoshi Tokusumi, Sayuri Seki, Takushi Nomura, Yusuke Takahara, Hiroshi Ishii, Tsugumine Shu, Hiromi Sakawaki, Hiroyuki Yamamoto |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
viruses 030106 microbiology lcsh:Medicine Viremia medicine.disease_cause Macaque Virus 03 medical and health sciences biology.animal medicine Cytotoxic T cell lcsh:Science Multidisciplinary biology business.industry lcsh:R virus diseases Simian immunodeficiency virus medicine.disease biology.organism_classification Virology Sendai virus Vaccination 030104 developmental biology lcsh:Q business Viral load |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-68267-w |
| Popis: | Anti-retroviral therapy (ART) can inhibit HIV proliferation but not achieve virus eradication from HIV-infected individuals. Under ART-based HIV control, virus-specific CD8+ T-cell responses are often reduced. Here, we investigated the impact of therapeutic vaccination inducing virus-specific CD8+ T-cell responses under ART on viral control in a macaque AIDS model. Twelve rhesus macaques received ART from week 12 to 32 after simian immunodeficiency virus (SIV) infection. Six of them were vaccinated with Sendai virus vectors expressing SIV Gag and Vif at weeks 26 and 32, and Gag/Vif-specific CD8+ T-cell responses were enhanced and became predominant. All macaques controlled viremia during ART but showed viremia rebound after ART cessation. Analysis of in vitro CD8+ cell ability to suppress replication of autologous lymphocytes-derived SIVs found augmentation of anti-SIV efficacy of CD8+ cells after vaccination. In the vaccinated animals, the anti-SIV efficacy of CD8+ cells at week 34 was correlated positively with Gag-specific CD8+ T-cell frequencies and inversely with rebound viral loads at week 34. These results indicate that Gag-specific CD8+ T-cell induction by therapeutic vaccination can augment anti-virus efficacy of CD8+ cells, which may be insufficient for functional cure but contribute to more stable viral control under ART. |
| Databáze: | OpenAIRE |
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