Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination.

Autor: Aydillo T; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. teresa.aydillo-gomez@mssm.edu.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. teresa.aydillo-gomez@mssm.edu., Gonzalez-Reiche AS; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Stadlbauer D; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Moderna, Cambridge, MA, USA., Amper MA; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Nair VD; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Mariottini C; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Sealfon SC; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., van Bakel H; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Palese P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. adolfo.garcia-sastre@mssm.edu.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. adolfo.garcia-sastre@mssm.edu.; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. adolfo.garcia-sastre@mssm.edu.; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. adolfo.garcia-sastre@mssm.edu.; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. adolfo.garcia-sastre@mssm.edu.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. adolfo.garcia-sastre@mssm.edu.
Jazyk: angličtina
Zdroj: NPJ vaccines [NPJ Vaccines] 2022 Dec 10; Vol. 7 (1), pp. 160. Date of Electronic Publication: 2022 Dec 10.
DOI: 10.1038/s41541-022-00583-w
Abstrakt: A phase 1 clinical trial to test the immunogenicity of a chimeric group 1 HA (cHA) universal influenza virus vaccine targeting the conserved stalk domain of the hemagglutinin of influenza viruses was carried out. Vaccination with adjuvanted-inactivated vaccines induced high anti-stalk antibody titers. We sought to identify gene expression signatures that correlate with such induction. Messenger-RNA sequencing in whole blood was performed on the peripheral blood of 53 vaccinees. We generated longitudinal data on the peripheral blood of 53 volunteers, at early (days 3 and 7) and late (28 days) time points after priming and boosting with cHAs. Differentially expressed gene analysis showed no differences between placebo and live-attenuated vaccine groups. However, an upregulation of genes involved in innate immune responses and type I interferon signaling was found at day 3 after vaccination with inactivated adjuvanted formulations. Cell type deconvolution analysis revealed a significant enrichment for monocyte markers and different subsets of dendritic cells as mediators for optimal B cell responses and significant increase of anti-stalk antibodies in sera. A significant upregulation of immunoglobulin-related genes was only observed after administration of adjuvanted vaccines (either as primer or booster) with specific induction of anti-stalk IGVH1-69. This approach informed of specific immune signatures that correlate with robust anti-stalk antibody responses, while also helping to understand the regulation of gene expression induced by cHA proteins under different vaccine regimens.
(© 2022. The Author(s).)
Databáze: MEDLINE
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