MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity
IntroductionVaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely unders...
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2024-12-01
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| author | Ilka Grewe Ilka Grewe Ilka Grewe Ilka Grewe Monika Friedrich Monika Friedrich Monika Friedrich Marie-Louise Dieck Marie-Louise Dieck Marie-Louise Dieck Michael Spohn Michael Spohn Michael Spohn My Linh Ly My Linh Ly My Linh Ly Verena Krähling Verena Krähling Leonie Mayer Leonie Mayer Leonie Mayer Sibylle C. Mellinghoff Sibylle C. Mellinghoff Sibylle C. Mellinghoff Monika Rottstegge Monika Rottstegge Monika Rottstegge Rebekka Kraemer Asisa Volz Asisa Volz Stephan Becker Stephan Becker Anahita Fathi Anahita Fathi Anahita Fathi Anahita Fathi Christine Dahlke Christine Dahlke Christine Dahlke Leonie M. Weskamm Leonie M. Weskamm Leonie M. Weskamm Marylyn M. Addo Marylyn M. Addo Marylyn M. Addo |
| author_facet | Ilka Grewe Ilka Grewe Ilka Grewe Ilka Grewe Monika Friedrich Monika Friedrich Monika Friedrich Marie-Louise Dieck Marie-Louise Dieck Marie-Louise Dieck Michael Spohn Michael Spohn Michael Spohn My Linh Ly My Linh Ly My Linh Ly Verena Krähling Verena Krähling Leonie Mayer Leonie Mayer Leonie Mayer Sibylle C. Mellinghoff Sibylle C. Mellinghoff Sibylle C. Mellinghoff Monika Rottstegge Monika Rottstegge Monika Rottstegge Rebekka Kraemer Asisa Volz Asisa Volz Stephan Becker Stephan Becker Anahita Fathi Anahita Fathi Anahita Fathi Anahita Fathi Christine Dahlke Christine Dahlke Christine Dahlke Leonie M. Weskamm Leonie M. Weskamm Leonie M. Weskamm Marylyn M. Addo Marylyn M. Addo Marylyn M. Addo |
| author_sort | Ilka Grewe |
| collection | DOAJ |
| description | IntroductionVaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely understood. Innate immune responses induced by viral vector vaccines are suggested to have an adjuvant effect for subsequent adaptive immunity. Integrating data on both innate and adaptive immunity, systems vaccinology approaches can improve the understanding of vaccine-induced immune mechanisms.MethodsTwo vaccine candidates against SARS-CoV-2, both based on the viral vector Modified Vaccinia virus Ankara (MVA) and encoding the native (MVA-SARS-2-S) or prefusion-stabilized spike protein (MVA-SARS-2-ST), were evaluated in phase 1 clinical trials (ClinicalTrials.gov: NCT04569383, NCT04895449). Longitudinal dynamics of innate and early adaptive immune responses induced by vaccination in SARS-CoV-2-naïve individuals were analyzed based on transcriptome and flow cytometry data, in comparison to the licensed ChAd and mRNA vaccines.ResultsCompared to MVA-SARS-2-S, MVA-SARS-2-ST (encoding the prefusion-stabilized spike protein) induced a stronger transcriptional activation early after vaccination, as well as higher virus neutralizing antibodies. Positive correlations were observed between innate and adaptive immune responses induced by a second MVA-SARS-2-ST vaccination. MVA-, ChAd- and mRNA-based vaccines induced distinct immune signatures, with the overall strongest transcriptional activation as well as monocyte and circulating T follicular helper (cTFH) cell responses induced by ChAd.DiscussionOur findings suggest a potential impact of the spike protein conformation not only on adaptive but also on innate immune responses. As indicated by positive correlations between several immune parameters induced by MVA-SARS-2-ST, the distinct transcriptional activation early after vaccination may be linked to the induction of classical monocytes and activation of cTFH1 cells, which may in turn result in the superior adaptive immunogenicity of MVA-SARS-2-ST, compared to MVA-SARS-2-S. Overall, our data demonstrate that both the vaccine platform and antigen insert can affect innate immune responses and subsequent vaccine immunogenicity in humans. |
| format | Article |
| id | doaj-art-29d8f2c5b4b44121a2c138e37cd7e347 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-29d8f2c5b4b44121a2c138e37cd7e3472025-08-20T02:37:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15006151500615MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunityIlka Grewe0Ilka Grewe1Ilka Grewe2Ilka Grewe3Monika Friedrich4Monika Friedrich5Monika Friedrich6Marie-Louise Dieck7Marie-Louise Dieck8Marie-Louise Dieck9Michael Spohn10Michael Spohn11Michael Spohn12My Linh Ly13My Linh Ly14My Linh Ly15Verena Krähling16Verena Krähling17Leonie Mayer18Leonie Mayer19Leonie Mayer20Sibylle C. Mellinghoff21Sibylle C. Mellinghoff22Sibylle C. Mellinghoff23Monika Rottstegge24Monika Rottstegge25Monika Rottstegge26Rebekka Kraemer27Asisa Volz28Asisa Volz29Stephan Becker30Stephan Becker31Anahita Fathi32Anahita Fathi33Anahita Fathi34Anahita Fathi35Christine Dahlke36Christine Dahlke37Christine Dahlke38Leonie M. Weskamm39Leonie M. Weskamm40Leonie M. Weskamm41Marylyn M. Addo42Marylyn M. Addo43Marylyn M. Addo44Institute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyFirst Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyGerman Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyGerman Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyGerman Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyResearch Institute Children’s Cancer Center Hamburg, Hamburg, GermanyDepartment of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyBioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyGerman Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyInstitute of Virology, Philipps University Marburg, Marburg, GermanyGerman Center for Infection Research, Partner Site Gießen-Marburg-Langen, Marburg, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyGerman Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany0Institute of Translational Research, Cluster of Excellence for Aging Research (CECAD), Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany1Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyGerman Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany2Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Medical Center Schleswig-Holstein, Kiel, Germany3Institute of Virology, University of Veterinary Medicine Hannover, Hanover, Germany4German Center for Infection Research, Partner Site Hannover-Braunschweig, Hannover, GermanyInstitute of Virology, Philipps University Marburg, Marburg, GermanyGerman Center for Infection Research, Partner Site Gießen-Marburg-Langen, Marburg, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyFirst Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyGerman Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyGerman Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyGerman Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyInstitute for Infection Research and Vaccine Development (IIRVD), Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment for Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyGerman Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, GermanyIntroductionVaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely understood. Innate immune responses induced by viral vector vaccines are suggested to have an adjuvant effect for subsequent adaptive immunity. Integrating data on both innate and adaptive immunity, systems vaccinology approaches can improve the understanding of vaccine-induced immune mechanisms.MethodsTwo vaccine candidates against SARS-CoV-2, both based on the viral vector Modified Vaccinia virus Ankara (MVA) and encoding the native (MVA-SARS-2-S) or prefusion-stabilized spike protein (MVA-SARS-2-ST), were evaluated in phase 1 clinical trials (ClinicalTrials.gov: NCT04569383, NCT04895449). Longitudinal dynamics of innate and early adaptive immune responses induced by vaccination in SARS-CoV-2-naïve individuals were analyzed based on transcriptome and flow cytometry data, in comparison to the licensed ChAd and mRNA vaccines.ResultsCompared to MVA-SARS-2-S, MVA-SARS-2-ST (encoding the prefusion-stabilized spike protein) induced a stronger transcriptional activation early after vaccination, as well as higher virus neutralizing antibodies. Positive correlations were observed between innate and adaptive immune responses induced by a second MVA-SARS-2-ST vaccination. MVA-, ChAd- and mRNA-based vaccines induced distinct immune signatures, with the overall strongest transcriptional activation as well as monocyte and circulating T follicular helper (cTFH) cell responses induced by ChAd.DiscussionOur findings suggest a potential impact of the spike protein conformation not only on adaptive but also on innate immune responses. As indicated by positive correlations between several immune parameters induced by MVA-SARS-2-ST, the distinct transcriptional activation early after vaccination may be linked to the induction of classical monocytes and activation of cTFH1 cells, which may in turn result in the superior adaptive immunogenicity of MVA-SARS-2-ST, compared to MVA-SARS-2-S. Overall, our data demonstrate that both the vaccine platform and antigen insert can affect innate immune responses and subsequent vaccine immunogenicity in humans.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500615/fullSARS-CoV-2COVID-19modified vaccinia virus Ankarasystems vaccinologyspike proteintranscriptome |
| spellingShingle | Ilka Grewe Ilka Grewe Ilka Grewe Ilka Grewe Monika Friedrich Monika Friedrich Monika Friedrich Marie-Louise Dieck Marie-Louise Dieck Marie-Louise Dieck Michael Spohn Michael Spohn Michael Spohn My Linh Ly My Linh Ly My Linh Ly Verena Krähling Verena Krähling Leonie Mayer Leonie Mayer Leonie Mayer Sibylle C. Mellinghoff Sibylle C. Mellinghoff Sibylle C. Mellinghoff Monika Rottstegge Monika Rottstegge Monika Rottstegge Rebekka Kraemer Asisa Volz Asisa Volz Stephan Becker Stephan Becker Anahita Fathi Anahita Fathi Anahita Fathi Anahita Fathi Christine Dahlke Christine Dahlke Christine Dahlke Leonie M. Weskamm Leonie M. Weskamm Leonie M. Weskamm Marylyn M. Addo Marylyn M. Addo Marylyn M. Addo MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity Frontiers in Immunology SARS-CoV-2 COVID-19 modified vaccinia virus Ankara systems vaccinology spike protein transcriptome |
| title | MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity |
| title_full | MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity |
| title_fullStr | MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity |
| title_full_unstemmed | MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity |
| title_short | MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity |
| title_sort | mva based sars cov 2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity |
| topic | SARS-CoV-2 COVID-19 modified vaccinia virus Ankara systems vaccinology spike protein transcriptome |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500615/full |
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