Systems biology analysis reveals distinct molecular signatures associated with immune responsiveness to the BNT162b COVID-19 vaccineResearch in context
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
Affiliations
Ivan Odak
Institute of Immunology, Hannover Medical School, Germany
Lennart Riemann
Institute 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, Germany
Inga Sandrock
Institute of Immunology, Hannover Medical School, Germany
Anne Cossmann
Department for Rheumatology and Immunology, Hannover Medical School, Germany
Gema Morillas Ramos
Department for Rheumatology and Immunology, Hannover Medical School, Germany
Swantje I. Hammerschmidt
Institute of Immunology, Hannover Medical School, Germany
Christiane Ritter
Institute of Immunology, Hannover Medical School, Germany
Michaela Friedrichsen
Institute of Immunology, Hannover Medical School, Germany
Ahmed Hassan
Institute of Immunology, Hannover Medical School, Germany
Alexandra Dopfer-Jablonka
Department for Rheumatology and Immunology, Hannover Medical School, Germany; German Center for Infection Research (DZIF), Partner Sites Hannover-Braunschweig, Germany
Metodi V. Stankov
Department for Rheumatology and Immunology, Hannover Medical School, Germany
Leonie M. Weskamm
Institute 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
Marylyn M. Addo
Institute 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, Germany
Inga Ravens
Institute of Immunology, Hannover Medical School, Germany
Stefanie Willenzon
Institute of Immunology, Hannover Medical School, Germany
Anja Schimrock
Institute of Immunology, Hannover Medical School, Germany
Jasmin Ristenpart
Institute of Immunology, Hannover Medical School, Germany
Anika Janssen
Institute of Immunology, Hannover Medical School, Germany
Joana Barros-Martins
Institute of Immunology, Hannover Medical School, Germany
Gesine Hansen
Department 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, Germany
Christine Falk
Institute for Transplantation Immunology, Hannover Medical School, Hannover, Germany
Georg M.N. Behrens
Department 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, Germany
Reinhold Förster
Institute 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.
