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SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8 + T-cells.
- Source :
-
Nature communications [Nat Commun] 2022 Aug 19; Vol. 13 (1), pp. 4888. Date of Electronic Publication: 2022 Aug 19. - 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.<br /> (© 2022. The Author(s).)
- Subjects :
- BNT162 Vaccine
CD4-Positive T-Lymphocytes
Granzymes
Humans
RNA, Messenger genetics
RNA, Messenger therapeutic use
SARS-CoV-2
Vaccination
Vaccines, Synthetic
Virus Latency
mRNA Vaccines
nef Gene Products, Human Immunodeficiency Virus genetics
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes virology
COVID-19 prevention & control
COVID-19 Vaccines immunology
HIV Infections immunology
HIV-1
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 35985993
- Full Text :
- https://doi.org/10.1038/s41467-022-32376-z