MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans
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
Affiliations
Leonie Mayer
Institute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf
Leonie M. Weskamm
Institute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf
Anahita Fathi
Institute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf
Maya Kono
Institute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf
Jasmin Heidepriem
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces
Verena Krähling
Institute for Virology, Philipps University Marburg
Sibylle C. Mellinghoff
Faculty 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 Cologne
My Linh Ly
Institute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf
Monika Friedrich
Institute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf
Svenja Hardtke
Institute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf
Saskia Borregaard
Clinical Trial Center North GmbH & Co. KG
Thomas Hesterkamp
German Centre for Infection Research, Translational Project Management Office
Felix F. Loeffler
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces
Asisa Volz
Institute of Virology, University of Veterinary Medicine Hannover, Foundation
Gerd Sutter
Division of Virology, Department of Veterinary Sciences, Institute for Infectious Diseases and Zoonoses, LMU Munich
Stephan Becker
Institute for Virology, Philipps University Marburg
Christine Dahlke
Institute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf
Marylyn M. Addo
Institute for Infection Research and Vaccine Development (IIRVD), University Medical Centre Hamburg-Eppendorf
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.
