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

Were R Omange1,2, Benjamin D Varco-Merth1,2, Omo Fadeyi1,2

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The Journal of Clinical Investigation
|January 29, 2026
PubMed
Summary

Boosting CD8+ T cells with mRNA vaccines before interrupting antiretroviral therapy (ART) delayed simian-human immunodeficiency virus (SIV) rebound in macaques. However, this immune boost did not provide long-term viral control after therapy interruption.

Keywords:
AIDS vaccineAIDS/HIVAdaptive immunityImmunology

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Area of Science:

  • Immunology
  • Vaccinology
  • Virology

Background:

  • CD8+ T cell responses are crucial for controlling viral infections like HIV/SIV.
  • Antiretroviral therapy (ART) interruption (ATI) typically leads to viral rebound due to insufficient T cell control.
  • Enhancing T cell responses at ATI may improve immune interception of reactivating SIV infections.

Purpose of the Study:

  • To determine if enhancing SIV-specific CD8+ T cells via mRNA vaccination prior to ATI improves immune control of SIV rebound.
  • To evaluate the impact of mRNA vaccines encoding SIV Gag, Nef, and Pol on viral load and rebound kinetics.

Main Methods:

  • SIVmac239-infected rhesus macaques (RMs) on ART were vaccinated with mRNA vaccines expressing SIV Gag, Nef, and Pol immediately before ATI.
  • Gag-specific CD8+ T cell responses were assessed in blood and lymphoid tissues.
  • Time to viral rebound and plasma viral loads (PVL) were monitored after ATI.

Main Results:

  • The mRNA/SIVgag vaccine successfully boosted Gag-specific CD8+ T cells.
  • Vaccination with mRNA/SIVgag, and mRNA/SIVgag + Nef + Pol, significantly delayed viral rebound and lowered PVL in the early weeks post-ATI compared to controls.
  • Long-term viral control was not achieved, with similar PVLs across groups by 24 weeks post-rebound.

Conclusions:

  • Boosting SIV-specific CD8+ T cells via mRNA vaccination at the time of ATI can enhance early immune targeting of reactivating SIV infections.
  • The observed viral control was transient, indicating that CD8+ T cell-targeting vaccines alone are insufficient for sustained virologic control.
  • Adjunctive therapies are necessary to improve the durability of virologic control elicited by CD8+ T cell-based vaccine strategies.