Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccineResearch in context
Summary: Background: Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying immune mechanisms for this remain largely unknown. Methods: Using a systems biology approach, we longitudinally profiled a unique cohort of female high and low respo...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423005133 |
| _version_ | 1797371448528994304 |
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| author | Ivan Odak Lennart Riemann Inga Sandrock Anne Cossmann Gema Morillas Ramos Swantje I. Hammerschmidt Christiane Ritter Michaela Friedrichsen Ahmed Hassan Alexandra Dopfer-Jablonka Metodi V. Stankov Leonie M. Weskamm Marylyn M. Addo Inga Ravens Stefanie Willenzon Anja Schimrock Jasmin Ristenpart Anika Janssen Joana Barros-Martins Gesine Hansen Christine Falk Georg M.N. Behrens Reinhold Förster |
| author_facet | Ivan Odak Lennart Riemann Inga Sandrock Anne Cossmann Gema Morillas Ramos Swantje I. Hammerschmidt Christiane Ritter Michaela Friedrichsen Ahmed Hassan Alexandra Dopfer-Jablonka Metodi V. Stankov Leonie M. Weskamm Marylyn M. Addo Inga Ravens Stefanie Willenzon Anja Schimrock Jasmin Ristenpart Anika Janssen Joana Barros-Martins Gesine Hansen Christine Falk Georg M.N. Behrens Reinhold Förster |
| author_sort | Ivan Odak |
| collection | DOAJ |
| description | Summary: Background: Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying immune mechanisms for this remain largely unknown. Methods: Using a systems biology approach, we longitudinally profiled a unique cohort of female high and low responders to the BNT162b vaccine, who were known from previous COVID-19 vaccinations to develop maximum and minimum immune responses to the vaccine. We utilized high dimensional flow cytometry, bulk and single cell mRNA sequencing and 48-plex serum cytokine analyses. Findings: We revealed early, transient immunological and molecular signatures that distinguished high from low responders and correlated with B and T cell responses measured 14 days later. High responders featured a distinct transcriptional activity of interferon-driven genes and genes connected to enhanced antigen presentation. This was accompanied by a robust cytokine response related to Th1 differentiation. Both transcriptome and serum cytokine signatures were confirmed in two independent confirmatory cohorts. Interpretation: Collectively, our data contribute to a better understanding of the immunogenicity of mRNA-based COVID-19 vaccines, which might lead to the optimization of vaccine designs for individuals with poor vaccine responses. Funding: German Center for Infection Research, German Center for Lung Research, German Research Foundation, Excellence Strategy EXC 2155 “RESIST” and European Regional Development Fund. |
| first_indexed | 2024-03-08T18:18:59Z |
| format | Article |
| id | doaj.art-dc942db6e492430cafa301d2bcc525b7 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-08T18:18:59Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-dc942db6e492430cafa301d2bcc525b72023-12-31T04:26:25ZengElsevierEBioMedicine2352-39642024-01-0199104947Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccineResearch in contextIvan Odak0Lennart Riemann1Inga Sandrock2Anne Cossmann3Gema Morillas Ramos4Swantje I. Hammerschmidt5Christiane Ritter6Michaela Friedrichsen7Ahmed Hassan8Alexandra Dopfer-Jablonka9Metodi V. Stankov10Leonie M. Weskamm11Marylyn M. Addo12Inga Ravens13Stefanie Willenzon14Anja Schimrock15Jasmin Ristenpart16Anika Janssen17Joana Barros-Martins18Gesine Hansen19Christine Falk20Georg M.N. Behrens21Reinhold Förster22Institute of Immunology, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, Germany; Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Germany; Clinician Scientist Program TITUS, Else-Kröner-Fresenius Foundation, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, GermanyDepartment for Rheumatology and Immunology, Hannover Medical School, GermanyDepartment for Rheumatology and Immunology, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, GermanyDepartment for Rheumatology and Immunology, Hannover Medical School, Germany; German Center for Infection Research (DZIF), Partner Sites Hannover-Braunschweig, GermanyDepartment for Rheumatology and Immunology, Hannover Medical School, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Department for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; German Centre for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Department for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; German Centre for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany; First Department of Medicine, Division of Infectious Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, GermanyInstitute of Immunology, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, GermanyInstitute of Immunology, Hannover Medical School, GermanyDepartment of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Germany; Clinician Scientist Program TITUS, Else-Kröner-Fresenius Foundation, Hannover Medical School, Germany; German Center of Lung Research (DZL), BREATH, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, GermanyInstitute for Transplantation Immunology, Hannover Medical School, Hannover, GermanyDepartment for Rheumatology and Immunology, Hannover Medical School, Germany; German Center for Infection Research (DZIF), Partner Sites Hannover-Braunschweig, Germany; Centre for Individualized Infection Medicine (CiiM), Hannover, GermanyInstitute of Immunology, Hannover Medical School, Germany; Clinician Scientist Program TITUS, Else-Kröner-Fresenius Foundation, Hannover Medical School, Germany; German Centre for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany; German Center of Lung Research (DZL), BREATH, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Germany; Corresponding author. Institute for Immunology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.Summary: Background: Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying immune mechanisms for this remain largely unknown. Methods: Using a systems biology approach, we longitudinally profiled a unique cohort of female high and low responders to the BNT162b vaccine, who were known from previous COVID-19 vaccinations to develop maximum and minimum immune responses to the vaccine. We utilized high dimensional flow cytometry, bulk and single cell mRNA sequencing and 48-plex serum cytokine analyses. Findings: We revealed early, transient immunological and molecular signatures that distinguished high from low responders and correlated with B and T cell responses measured 14 days later. High responders featured a distinct transcriptional activity of interferon-driven genes and genes connected to enhanced antigen presentation. This was accompanied by a robust cytokine response related to Th1 differentiation. Both transcriptome and serum cytokine signatures were confirmed in two independent confirmatory cohorts. Interpretation: Collectively, our data contribute to a better understanding of the immunogenicity of mRNA-based COVID-19 vaccines, which might lead to the optimization of vaccine designs for individuals with poor vaccine responses. Funding: German Center for Infection Research, German Center for Lung Research, German Research Foundation, Excellence Strategy EXC 2155 “RESIST” and European Regional Development Fund.http://www.sciencedirect.com/science/article/pii/S2352396423005133BNT162bmRNA vaccineSystems biologyMonocytes |
| spellingShingle | Ivan Odak Lennart Riemann Inga Sandrock Anne Cossmann Gema Morillas Ramos Swantje I. Hammerschmidt Christiane Ritter Michaela Friedrichsen Ahmed Hassan Alexandra Dopfer-Jablonka Metodi V. Stankov Leonie M. Weskamm Marylyn M. Addo Inga Ravens Stefanie Willenzon Anja Schimrock Jasmin Ristenpart Anika Janssen Joana Barros-Martins Gesine Hansen Christine Falk Georg M.N. Behrens Reinhold Förster Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccineResearch in context EBioMedicine BNT162b mRNA vaccine Systems biology Monocytes |
| title | Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccineResearch in context |
| title_full | Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccineResearch in context |
| title_fullStr | Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccineResearch in context |
| title_full_unstemmed | Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccineResearch in context |
| title_short | Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccineResearch in context |
| title_sort | systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the bnt162b covid 19 vaccineresearch in context |
| topic | BNT162b mRNA vaccine Systems biology Monocytes |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423005133 |
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