Your browser doesn't support javascript.
SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells.
Stevenson, Eva M; Terry, Sandra; Copertino, Dennis; Leyre, Louise; Danesh, Ali; Weiler, Jared; Ward, Adam R; Khadka, Pragya; McNeil, Evan; Bernard, Kevin; Miller, Itzayana G; Ellsworth, Grant B; Johnston, Carrie D; Finkelsztein, Eli J; Zumbo, Paul; Betel, Doron; Dündar, Friederike; Duncan, Maggie C; Lapointe, Hope R; Speckmaier, Sarah; Moran-Garcia, Nadia; Papa, Michelle Premazzi; Nicholes, Samuel; Stover, Carissa J; Lynch, Rebecca M; Caskey, Marina; Gaebler, Christian; Chun, Tae-Wook; Bosque, Alberto; Wilkin, Timothy J; Lee, Guinevere Q; Brumme, Zabrina L; Jones, R Brad.
  • Stevenson EM; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Terry S; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Copertino D; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Leyre L; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Danesh A; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.
  • Weiler J; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Ward AR; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Khadka P; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • McNeil E; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Bernard K; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Miller IG; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Ellsworth GB; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Johnston CD; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Finkelsztein EJ; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Zumbo P; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Betel D; Applied Bioinformatics Core, Weill Cornell Medical College, New York, NY, USA.
  • Dündar F; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
  • Duncan MC; Applied Bioinformatics Core, Weill Cornell Medical College, New York, NY, USA.
  • Lapointe HR; Applied Bioinformatics Core, Weill Cornell Medical College, New York, NY, USA.
  • Speckmaier S; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA.
  • Moran-Garcia N; Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
  • Papa MP; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
  • Nicholes S; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
  • Stover CJ; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
  • Lynch RM; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
  • Caskey M; Dept of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
  • Gaebler C; Dept of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
  • Chun TW; Dept of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
  • Bosque A; Dept of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
  • Wilkin TJ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Lee GQ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
  • Brumme ZL; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID, NIH, Bethesda, MD, USA.
  • Jones RB; Dept of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
Nat Commun ; 13(1): 4888, 2022 08 19.
Article in English | MEDLINE | ID: covidwho-2000886
ABSTRACT
Efforts to cure HIV have focused on reactivating latent proviruses to enable elimination by CD8+ 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+ 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+ 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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: HIV Infections / HIV-1 / CD8-Positive T-Lymphocytes / COVID-19 Vaccines / COVID-19 Type of study: Observational study / Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-32376-z

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: HIV Infections / HIV-1 / CD8-Positive T-Lymphocytes / COVID-19 Vaccines / COVID-19 Type of study: Observational study / Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-32376-z