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SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells.
- Source :
- Nature Communications; 8/19/2022, Vol. 13 Issue 1, p1-15, 15p
- Publication Year :
- 2022
-
Abstract
- Efforts to cure HIV have focused on reactivating latent proviruses to enable elimination by CD8<superscript>+</superscript> cytotoxic T-cells. Clinical studies of latency reversing agents (LRA) in antiretroviral therapy (ART)-treated individuals have shown increases in HIV transcription, but without reductions in virologic measures, or evidence that HIV-specific CD8<superscript>+</superscript> T-cells were productively engaged. Here, we show that the SARS-CoV-2 mRNA vaccine BNT162b2 activates the RIG-I/TLR – TNF – NFκb axis, resulting in transcription of HIV proviruses with minimal perturbations of T-cell activation and host transcription. T-cells specific for the early gene-product HIV-Nef uniquely increased in frequency and acquired effector function (granzyme-B) in ART-treated individuals following SARS-CoV-2 mRNA vaccination. These parameters of CD8<superscript>+</superscript> T-cell induction correlated with significant decreases in cell-associated HIV mRNA, suggesting killing or suppression of cells transcribing HIV. Thus, we report the observation of an intervention-induced reduction in a measure of HIV persistence, accompanied by precise immune correlates, in ART-suppressed individuals. However, we did not observe significant depletions of intact proviruses, underscoring challenges to achieving (or measuring) HIV reservoir reductions. Overall, our results support prioritizing the measurement of granzyme-B-producing Nef-specific responses in latency reversal studies and add impetus to developing HIV-targeted mRNA therapeutic vaccines that leverage built-in LRA activity. Here, the authors show in a cohort of people with HIV, COVID mRNA vaccination is followed by a transient boost in a particular profile of HIV-specific T-cell responses and a corresponding decrease in residual HIV RNA – suggesting productive immune engagement with infected cells. [ABSTRACT FROM AUTHOR]
- Subjects :
- SARS-CoV-2
HIV
COVID-19 vaccines
CYTOTOXIC T cells
MESSENGER RNA
T cells
VACCINATION
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 13
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 158651809
- Full Text :
- https://doi.org/10.1038/s41467-022-32376-z