Boosting SIV-specific CD8+ T cell responses prior to ART interruption extends time to SIVmac239 rebound

Year: 2026

Type: article

Abstract: HIV/SIV-specific CD8+ T cell responses are typically unable to control viral rebound following antiretroviral therapy (ART) interruption (ATI). To investigate whether enhancing the magnitude and activation of SIV-specific CD8+ T cells at the time of ATI can improve the immune interception of reactivating SIV infections, we vaccinated SIVmac239-infected rhesus macaques (RMs) on ART, boosting immediately prior to ATI, with a nucleoside-unmodified mRNA vaccine expressing SIVmac239 Gag (mRNA/SIVgag) alone or in combination with Nef (mRNA/SIVnef) and Pol (mRNA/SIVpol). The mRNA/SIVgag vaccine was effective in boosting Gag-specific CD8+ T cells in blood and lymphoid tissues. Following ATI, the mRNA/SIVgag vaccine group showed a significant delay in time to measurable viral rebound compared with controls and manifested lower plasma viral loads (PVLs) for up to 6 weeks after rebound. Similarly, RMs that received mRNA/SIVgag, mRNA/SIVnef, and mRNA/SIVpol also manifested a delay in SIV rebound compared with controls, suggesting that boosting SIV-specific CD8+ T cells during ATI can enhance early immune targeting of reactivating SIV infections. However, viral control was not sustained long term as PVLs were similar across vaccinees and controls by 24 weeks after rebound, highlighting the need for adjunctive therapies to improve the durability of virologic control elicited by CD8+ T cell-targeting vaccines.

Source: Journal of Clinical Investigation

DOI: 10.1172/jci198294

Institutions: Oregon National Primate Research Center, Oregon Health & Science University, Vaccine and Gene Therapy Institute, Frederick National Laboratory for Cancer Research, Fred Hutch Cancer Center, CureVac (Germany)

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,200

Funders: U.S. Department of Health and Human Services, Gilead Sciences, Emory University, National Institutes of Health, Oregon National Primate Research Center, NIH Office of the Director, National Cancer Institute, National Institute of Allergy and Infectious Diseases

Awards: G104308456, G1234541941, G1294778923, G1395940287, G2415337126, G3674451543, G4689185066, G5546697591, G6252953675, Development of an mRNA-Based Therapeutic HIV/AIDS Vaccine, G9000003089

OpenAlex ID: W7126041740