@article{ede0b0d6a66749abba74b333d1c57d34,
title = "Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination",
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.",
author = "Teresa Aydillo and Gonzalez-Reiche, {Ana S.} and Daniel Stadlbauer and Amper, {Mary Anne} and Nair, {Venugopalan D.} and Chiara Mariottini and Sealfon, {Stuart C.} and {van Bakel}, Harm and Peter Palese and Florian Krammer and Adolfo Garc{\'i}a-Sastre",
note = "Funding Information: We thank Richard Cadagan for excellent technical assistance and Raffael Nachbagauer for providing access to samples and data. This clinical trial (NCT03300050) was funded in part by the Bill and Melinda Gates Foundation (grant OPP1084518). Basic research leading to this trial was supported by the National Institute of Allergy and Infectious Diseases (NIAID) (grants P01 AI097092, HHSN26620070010C, HHSN272201400008C, U19 AI109946, R01 AI128821). This work was funded by the NIAID through the Collaborative Influenza Vaccine Innovation Centers contract (CIVIC, 75N93019C00051), the Centers of Excellence for Influenza Research and Response contract (CEIRR, 75N93019R00028) and U19AI135972 grant. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD026880. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: We thank Richard Cadagan for excellent technical assistance and Raffael Nachbagauer for providing access to samples and data. This clinical trial (NCT03300050) was funded in part by the Bill and Melinda Gates Foundation (grant OPP1084518). Basic research leading to this trial was supported by the National Institute of Allergy and Infectious Diseases (NIAID) (grants P01 AI097092, HHSN26620070010C, HHSN272201400008C, U19 AI109946, R01 AI128821). This work was funded by the NIAID through the Collaborative Influenza Vaccine Innovation Centers contract (CIVIC, 75N93019C00051), the Centers of Excellence for Influenza Research and Response contract (CEIRR, 75N93019R00028) and U19AI135972 grant. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD026880. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: The Icahn School of Medicine at Mount Sinai (ISMMS) has issued patents and filed patent applications covering the use of chimeric hemagglutinin antigens as vaccines. A.G.-S., P.P., and F.K. are named as inventors on these patents and applications. The ISMMS and the inventors have received payments as consideration for these rights. The laboratories of A.G.-S., P.P., and F.K. were also engaged in a research program that was funded by GlaxoSmithKline Biologicals SA. All other authors declare no competing interests. The A.G.-S. laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, Paratus, CureLab Oncology, CureLab Veterinary and Pfizer, outside of the reported work. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41541-022-00583-w",
language = "English",
volume = "7",
journal = "npj Vaccines",
issn = "2059-0105",
publisher = "Nature Publishing Group",
number = "1",
}