Boosting SIV-specific CD8+ T cell responses prior to ART interruption extends time to SIVmac239 rebound
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.
Authors
- Susanne Rauch (ORCID: https://orcid.org/0009-0008-4587-5384)
- Hideaki Takata (ORCID: https://orcid.org/0000-0001-9436-1517)
- Christine M. Fennessey (ORCID: https://orcid.org/0000-0002-8736-8523)
- Randy Fast (ORCID: https://orcid.org/0000-0003-3042-9214)
- B. Keele
- Rhonda MacAllister (ORCID: https://orcid.org/0000-0002-9937-7662)
- William J. Bosche (ORCID: https://orcid.org/0000-0001-5367-2116)
- Alejandra Marenco
- Benjamin Petsch (ORCID: https://orcid.org/0000-0001-7431-0683)
- Derick M. Duell
- Emek Köse (ORCID: https://orcid.org/0009-0001-9234-581X)
- Ewelina Kosmider
- Janina Gergen
- Rebecca Shoemaker
- Rachele M. Bochart (ORCID: https://orcid.org/0000-0001-9795-6516)
- J. Lifson
- K. Oswald
- Taina T. Immonen (ORCID: https://orcid.org/0000-0003-4521-0696)
- Louis J. Picker (ORCID: https://orcid.org/0000-0003-0546-398X)
- Jeremy Smedley (ORCID: https://orcid.org/0000-0003-3369-4662)
- Benjamin D. Varco-Merth
- Paul T. Edlefsen
- Michael K. Axthelm
- Omo Fadeyi
- Caralyn S. Labriola
- Paula Armitage
- William D. Goodwin
- Were R. Omange
- Chris Homick
- Afam A. Okoye
Institutions
- Oregon National Primate Research Center (US)
- Oregon Health & Science University (US)
- Fred Hutch Cancer Center (US)
- CureVac (Germany) (DE)
- Frederick National Laboratory for Cancer Research (US)
- Vaccine and Gene Therapy Institute
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2026-01-29
- DOI
- https://doi.org/10.1172/jci198294
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
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