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The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination.
Wimmers, Florian; Donato, Michele; Kuo, Alex; Ashuach, Tal; Gupta, Shakti; Li, Chunfeng; Dvorak, Mai; Foecke, Mariko Hinton; Chang, Sarah E; Hagan, Thomas; De Jong, Sanne E; Maecker, Holden T; van der Most, Robbert; Cheung, Peggie; Cortese, Mario; Bosinger, Steven E; Davis, Mark; Rouphael, Nadine; Subramaniam, Shankar; Yosef, Nir; Utz, Paul J; Khatri, Purvesh; Pulendran, Bali.
  • Wimmers F; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Donato M; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Kuo A; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Ashuach T; Department of Electrical Engineering and Computer Sciences and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Gupta S; Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive MC 0412, La Jolla, CA 92093, USA.
  • Li C; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Dvorak M; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Foecke MH; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Chang SE; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Hagan T; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • De Jong SE; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Maecker HT; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • van der Most R; GSK, 1330 Rixensart, Belgium.
  • Cheung P; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Cortese M; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Bosinger SE; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Davis M; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305
  • Rouphael N; Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
  • Subramaniam S; Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive MC 0412, La Jolla, CA 92093, USA.
  • Yosef N; Department of Electrical Engineering and Computer Sciences and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Chan-Zuckerberg Biohub, San Francisco, CA, USA.
  • Utz PJ; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Khatri P; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Pulendran B; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanfor
Cell ; 184(15): 3915-3935.e21, 2021 07 22.
Article in English | MEDLINE | ID: covidwho-1283262
ABSTRACT
Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza induced persistently diminished H3K27ac in monocytes and myeloid dendritic cells (mDCs), which was associated with impaired cytokine responses to Toll-like receptor stimulation. Single-cell ATAC-seq analysis revealed an epigenomically distinct subcluster of monocytes with reduced chromatin accessibility at AP-1-targeted loci after vaccination. Similar effects were observed in response to vaccination with the AS03-adjuvanted H5N1 pandemic influenza vaccine. However, this vaccine also stimulated persistently increased chromatin accessibility at interferon response factor (IRF) loci in monocytes and mDCs. This was associated with elevated expression of antiviral genes and heightened resistance to the unrelated Zika and Dengue viruses. These results demonstrate that vaccination stimulates persistent epigenomic remodeling of the innate immune system and reveal AS03's potential as an epigenetic adjuvant.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Transcription, Genetic / Influenza Vaccines / Vaccination / Single-Cell Analysis / Epigenomics / Immunity Type of study: Controlled clinical trial / Randomized controlled trials Topics: Vaccines Limits: Adolescent / Adult / Female / Humans / Male / Young adult Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.05.039

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Transcription, Genetic / Influenza Vaccines / Vaccination / Single-Cell Analysis / Epigenomics / Immunity Type of study: Controlled clinical trial / Randomized controlled trials Topics: Vaccines Limits: Adolescent / Adult / Female / Humans / Male / Young adult Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.05.039