Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
10 Dec 2022
10 Dec 2022
Historique:
received:
11
04
2022
accepted:
25
11
2022
entrez:
10
12
2022
pubmed:
11
12
2022
medline:
11
12
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36496417
doi: 10.1038/s41541-022-00583-w
pii: 10.1038/s41541-022-00583-w
pmc: PMC9741632
doi:
Types de publication
Journal Article
Langues
eng
Pagination
160Subventions
Organisme : NIAID NIH HHS
ID : U19 AI135972
Pays : United States
Informations de copyright
© 2022. The Author(s).
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