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

Teresa Aydillo, Ana S. Gonzalez-Reiche, Daniel Stadlbauer, Mary Anne Amper, Venugopalan D. Nair, Chiara Mariottini, Stuart C. Sealfon, Harm van Bakel, Peter Palese, Florian Krammer, Adolfo García-Sastre

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish
Article number160
Journalnpj Vaccines
Volume7
Issue number1
DOIs
StatePublished - Dec 2022

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