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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/SIV-Gag vaccine group showed a significant delay in time to measurable viral rebound compared to controls, and manifested lower plasma viral loads (PVL) 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 to 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 post-rebound, highlighting the need for adjunctive therapies to improve the durability of virologic control elicited by CD8+ T cell-targeting vaccines.
Authors
Were R. Omange, Benjamin D. Varco-Merth, Omo Fadeyi, Alejandra Marenco, Hiroshi Takata, Derick M. Duell, William D. Goodwin, Paula Armitage, Christine M. Fennessey, Emek Kose, Taina T. Immonen, Ewelina Kosmider, William J. Bosche, Randy Fast, Chris Homick, Kelli Oswald, Rebecca Shoemaker, Rachele Bochart, Rhonda MacAllister, Caralyn S. Labriola, Jeremy V. Smedley, Michael K. Axthelm, Paul T. Edlefsen, Brandon F. Keele, Jeffrey D. Lifson, Janina Gergen, Benjamin Petsch, Susanne Rauch, Louis J. Picker, Afam A. Okoye
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ISSN: 0021-9738 (print), 1558-8238 (online)