Longitudinal multiomic profiling and corticosteroid modulation of the immediate innate immune response to an adenovirus-vector vaccine

Vaccine. 2024 Nov 14;42(25):126118. doi: 10.1016/j.vaccine.2024.07.019. Epub 2024 Jul 18.

Abstract

Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.

Keywords: COVID-19; Innate immunity; Vaccine; Vector.

MeSH terms

  • Adrenal Cortex Hormones
  • Adult
  • Animals
  • COVID-19 / immunology
  • COVID-19 / prevention & control
  • COVID-19 Vaccines* / immunology
  • ChAdOx1 nCoV-19* / immunology
  • Female
  • Genetic Vectors / genetics
  • Humans
  • Immunity, Innate*
  • Immunogenicity, Vaccine
  • Male
  • Monocytes / immunology
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocytes / immunology
  • Vaccination / methods

Substances

  • COVID-19 Vaccines
  • ChAdOx1 nCoV-19
  • Adrenal Cortex Hormones
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2