Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination
Year: 2022
Type: article
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.
Source: npj Vaccines
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,390
Awards: G103575219, G138343377, Antibody responses in humans after infection with avian influenza viruses, Mechanisms of broadly neutralizing humoral immunity against influenza viruses, G2961843849, G3489368955, Toward a Universal Influenza Virus Vaccine, Big Omics Data Engine 2 Supercomputer, G4102728913, G4881636923, G5374026869, G5982071039, G6526191098, G6627348897, G6795096461, G7059131728, G7424451958, COVID and Translational Science supercomputer (CATS), G9000349350, SARS-CoV adaptations through a Systems Biology Lens (SYBIL)
OpenAlex ID: W4311501976