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

• Published in: Vaccine 2024-11, Vol.42 (25), p.126118, Article 126118
• Main Authors: Jin Choi, Seong, Lee, Wonhyo, Cheol Kim, Sang, Jo, Hye-Yeong, Park, Hyun-Young, Bin Kim, Hong, Park, Woong-Yang, Ho Park, Sung, Ko, Jae-Hoon, Seok Lee, Jeong
• Format: Article
• Language: English
• Subjects: Adenoviruses; Adrenal Cortex Hormones; Adult; Animals; Antibodies; Bar codes; ChAdOx1 nCoV-19 - immunology; Chromatin; Corticoids; Corticosteroids; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - immunology; Female; Genes; Genetic Vectors - genetics; Genomes; Genomics; Humans; Immune response; Immune system; Immunity, Innate; Immunogenicity; Immunogenicity, Vaccine; Immunomodulation; Inflammation; Innate immunity; Lymphocytes; Lymphocytes T; Male; Monkeys & apes; Monocytes; Monocytes - immunology; Pandemics; Production costs; Proteins; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Side effects; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Steroids; T-Lymphocytes - immunology; Transcriptomes; Vaccination - methods; Vaccine; Vaccines; Vector
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2024.07.019

Longitudinal multiomic (single cell transcriptome/TCR/BCR, CD14 + ATAC) immune landscape following ChAdOx1 nCoV-19 vaccination. Monocyte and innate-like T cell populations expressing interferon-stimulated genes increased 1 day post-vaccination, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these inflammatory responses without hampering vaccine immunogenicity. [Display omitted] 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.