Env-independent protection of intrarectal SIV challenge by vaccine induction of Gag/Vif-specific CD8+ T cells but not CD4+ T cells.

Effective T cell induction is an important strategy in HIV-vaccine development. However, it has been indicated that vaccine-induced HIV-specific CD4+ T cells, the preferential targets of HIV infection, might increase viral acquisition after HIV exposure. We have recently developed an immunogen (CaV11), tandemly connected overlapping 11-mer peptides spanning the simian immunodeficiency virus (SIV) Gag capsid and Vif proteins, to selectively induce Gag- and Vif-specific CD8+ T cells but not CD4+ T cells. Here, we show protective efficacy of a CaV11-expressing vaccine against repeated intrarectal low-dose SIVmac239 challenge in rhesus macaques. Eight of the twelve vaccinated macaques were protected after eight challenges. Kaplan-Meier analysis indicated significant protection in the vaccinees compared to the unvaccinated macaques. Vaccine-induced Gag-specific CD8+ T cell responses were significantly higher in the protected than the unprotected vaccinees. These results suggest that classical CD8+ T cell induction by viral Env-independent vaccination can confer protection from intrarectal SIV acquisition, highlighting the rationale for this immunogen design to induce virus-specific CD8+ T cells but not CD4+ T cells in HIV-vaccine development. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Hiroshi Ishii, Kazutaka Terahara, Takushi Nomura, Midori Okazaki, Hiroyuki Yamamoto, Tsugumine Shu, Hiromi Sakawaki, Tomoyuki Miura, David I Watkins, Tetsuro Matano. Env-independent protection of intrarectal SIV challenge by vaccine induction of Gag/Vif-specific CD8+ T cells but not CD4+ T cells. Molecular therapy : the journal of the American Society of Gene Therapy. 2022 Feb 26;30(5):2048-2057

Mesh Tags

Substances

PMID: 35231604

search → result