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 antib...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-12-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-022-00583-w |
| _version_ | 1797429429197078528 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Teresa Aydillo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T09:13:03Z |
| format | Article |
| id | doaj.art-8b794dc1a4914540906c55991b10614c |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T09:13:03Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-8b794dc1a4914540906c55991b10614c2023-12-02T08:11:48ZengNature Portfolionpj Vaccines2059-01052022-12-017111410.1038/s41541-022-00583-wTranscriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccinationTeresa Aydillo0Ana S. Gonzalez-Reiche1Daniel Stadlbauer2Mary Anne Amper3Venugopalan D. Nair4Chiara Mariottini5Stuart C. Sealfon6Harm van Bakel7Peter Palese8Florian Krammer9Adolfo García-Sastre10Department of Microbiology, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiDepartment of Microbiology, Icahn School of Medicine at Mount SinaiDepartment of Neurology, Icahn School of Medicine at Mount SinaiDepartment of Neurology, Icahn School of Medicine at Mount SinaiDepartment of Microbiology, Icahn School of Medicine at Mount SinaiDepartment of Neurology, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomics Sciences, Icahn School of Medicine at Mount SinaiDepartment of Microbiology, Icahn School of Medicine at Mount SinaiDepartment of Microbiology, Icahn School of Medicine at Mount SinaiDepartment of Microbiology, Icahn School of Medicine at Mount SinaiAbstract 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.https://doi.org/10.1038/s41541-022-00583-w |
| spellingShingle | 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 Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination npj Vaccines |
| title | Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination |
| title_full | Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination |
| title_fullStr | Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination |
| title_full_unstemmed | Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination |
| title_short | Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination |
| title_sort | transcriptome signatures preceding the induction of anti stalk antibodies elicited after universal influenza vaccination |
| url | https://doi.org/10.1038/s41541-022-00583-w |
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