MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans
Abstract In response to the COVID-19 pandemic, multiple vaccines were developed using platforms such as viral vectors and mRNA technology. Here, we report humoral and cellular immunogenicity data from human phase 1 clinical trials investigating two recombinant Modified Vaccinia virus Ankara vaccine...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00801-z |
| _version_ | 1797340346462502912 |
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| author | Leonie Mayer Leonie M. Weskamm Anahita Fathi Maya Kono Jasmin Heidepriem Verena Krähling Sibylle C. Mellinghoff My Linh Ly Monika Friedrich Svenja Hardtke Saskia Borregaard Thomas Hesterkamp Felix F. Loeffler Asisa Volz Gerd Sutter Stephan Becker Christine Dahlke Marylyn M. Addo |
| author_facet | Leonie Mayer Leonie M. Weskamm Anahita Fathi Maya Kono Jasmin Heidepriem Verena Krähling Sibylle C. Mellinghoff My Linh Ly Monika Friedrich Svenja Hardtke Saskia Borregaard Thomas Hesterkamp Felix F. Loeffler Asisa Volz Gerd Sutter Stephan Becker Christine Dahlke Marylyn M. Addo |
| author_sort | Leonie Mayer |
| collection | DOAJ |
| description | Abstract In response to the COVID-19 pandemic, multiple vaccines were developed using platforms such as viral vectors and mRNA technology. Here, we report humoral and cellular immunogenicity data from human phase 1 clinical trials investigating two recombinant Modified Vaccinia virus Ankara vaccine candidates, MVA-SARS-2-S and MVA-SARS-2-ST, encoding the native and the prefusion-stabilized SARS-CoV-2 spike protein, respectively. MVA-SARS-2-ST was more immunogenic than MVA-SARS-2-S, but both were less immunogenic compared to licensed mRNA- and ChAd-based vaccines in SARS-CoV-2 naïve individuals. In heterologous vaccination, previous MVA-SARS-2-S vaccination enhanced T cell functionality and MVA-SARS-2-ST boosted the frequency of T cells and S1-specific IgG levels when used as a third vaccination. While the vaccine candidate containing the prefusion-stabilized spike elicited predominantly S1-specific responses, immunity to the candidate with the native spike was skewed towards S2-specific responses. These data demonstrate how the spike antigen conformation, using the same viral vector, directly affects vaccine immunogenicity in humans. |
| first_indexed | 2024-03-08T10:00:47Z |
| format | Article |
| id | doaj.art-5b1fea1ceb2340e395b1e673ec685d27 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-08T10:00:47Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-5b1fea1ceb2340e395b1e673ec685d272024-01-29T10:55:53ZengNature Portfolionpj Vaccines2059-01052024-01-019111410.1038/s41541-023-00801-zMVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humansLeonie Mayer0Leonie M. Weskamm1Anahita Fathi2Maya Kono3Jasmin Heidepriem4Verena Krähling5Sibylle C. Mellinghoff6My Linh Ly7Monika Friedrich8Svenja Hardtke9Saskia Borregaard10Thomas Hesterkamp11Felix F. Loeffler12Asisa Volz13Gerd Sutter14Stephan Becker15Christine Dahlke16Marylyn M. Addo17Institute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-EppendorfInstitute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-EppendorfInstitute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-EppendorfInstitute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-EppendorfDepartment of Biomolecular Systems, Max Planck Institute of Colloids and InterfacesInstitute for Virology, Philipps University MarburgFaculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, Centre for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), German CLL Group (GCLLSG), University of CologneInstitute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-EppendorfInstitute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-EppendorfInstitute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-EppendorfClinical Trial Center North GmbH & Co. KGGerman Centre for Infection Research, Translational Project Management OfficeDepartment of Biomolecular Systems, Max Planck Institute of Colloids and InterfacesInstitute of Virology, University of Veterinary Medicine Hannover, FoundationDivision of Virology, Department of Veterinary Sciences, Institute for Infectious Diseases and Zoonoses, LMU MunichInstitute for Virology, Philipps University MarburgInstitute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-EppendorfInstitute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-EppendorfAbstract In response to the COVID-19 pandemic, multiple vaccines were developed using platforms such as viral vectors and mRNA technology. Here, we report humoral and cellular immunogenicity data from human phase 1 clinical trials investigating two recombinant Modified Vaccinia virus Ankara vaccine candidates, MVA-SARS-2-S and MVA-SARS-2-ST, encoding the native and the prefusion-stabilized SARS-CoV-2 spike protein, respectively. MVA-SARS-2-ST was more immunogenic than MVA-SARS-2-S, but both were less immunogenic compared to licensed mRNA- and ChAd-based vaccines in SARS-CoV-2 naïve individuals. In heterologous vaccination, previous MVA-SARS-2-S vaccination enhanced T cell functionality and MVA-SARS-2-ST boosted the frequency of T cells and S1-specific IgG levels when used as a third vaccination. While the vaccine candidate containing the prefusion-stabilized spike elicited predominantly S1-specific responses, immunity to the candidate with the native spike was skewed towards S2-specific responses. These data demonstrate how the spike antigen conformation, using the same viral vector, directly affects vaccine immunogenicity in humans.https://doi.org/10.1038/s41541-023-00801-z |
| spellingShingle | Leonie Mayer Leonie M. Weskamm Anahita Fathi Maya Kono Jasmin Heidepriem Verena Krähling Sibylle C. Mellinghoff My Linh Ly Monika Friedrich Svenja Hardtke Saskia Borregaard Thomas Hesterkamp Felix F. Loeffler Asisa Volz Gerd Sutter Stephan Becker Christine Dahlke Marylyn M. Addo MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans npj Vaccines |
| title | MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans |
| title_full | MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans |
| title_fullStr | MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans |
| title_full_unstemmed | MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans |
| title_short | MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans |
| title_sort | mva based vaccine candidates encoding the native or prefusion stabilized sars cov 2 spike reveal differential immunogenicity in humans |
| url | https://doi.org/10.1038/s41541-023-00801-z |
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