Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome

Anahita Fathi, Christine Dahlke, Verena Krähling, Alexandra Kupke, Nisreen M. A. Okba, Matthijs P. Raadsen, Jasmin Heidepriem, Marcel A. Müller, Grigori Paris, Susan Lassen, Michael Klüver, Asisa Volz, Till Koch, My L. Ly, Monika Friedrich, Robert Fux, Alina Tscherne, Georgia Kalodimou, Stefan Schmiedel, Victor M. Corman, Thomas Hesterkamp, Christian Drosten, Felix F. Loeffler, Bart L. Haagmans, Gerd Sutter, Stephan Becker and Marylyn M. Addo ()
Additional contact information
Anahita Fathi: University Medical Center Hamburg-Eppendorf, Institute for Infection Research and Vaccine Development (IIRVD)
Christine Dahlke: University Medical Center Hamburg-Eppendorf, Institute for Infection Research and Vaccine Development (IIRVD)
Verena Krähling: Philipps University Marburg, Institute of Virology
Alexandra Kupke: Philipps University Marburg, Institute of Virology
Nisreen M. A. Okba: Erasmus Medical Center, Department of Viroscience
Matthijs P. Raadsen: Erasmus Medical Center, Department of Viroscience
Jasmin Heidepriem: Max Planck Institute of Colloids and Interfaces, Department of Biomolecular Systems
Marcel A. Müller: Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology
Grigori Paris: Max Planck Institute of Colloids and Interfaces, Department of Biomolecular Systems
Susan Lassen: University Medical Center Hamburg-Eppendorf, Institute for Infection Research and Vaccine Development (IIRVD)
Michael Klüver: Philipps University Marburg, Institute of Virology
Asisa Volz: University of Veterinary Medicine Hanover, Institute of Virology
Till Koch: Bernhard-Nocht-Institute for Tropical Medicine, Department for Clinical Immunology of Infectious Diseases
My L. Ly: University Medical Center Hamburg-Eppendorf, Institute for Infection Research and Vaccine Development (IIRVD)
Monika Friedrich: University Medical Center Hamburg-Eppendorf, Institute for Infection Research and Vaccine Development (IIRVD)
Robert Fux: LMU University of Munich, Institute of Infectious Diseases and Zoonoses
Alina Tscherne: LMU University of Munich, Institute of Infectious Diseases and Zoonoses
Georgia Kalodimou: LMU University of Munich, Institute of Infectious Diseases and Zoonoses
Stefan Schmiedel: German Center for Infection Research, partner site Hamburg-Lübeck-Borstel-Riems
Victor M. Corman: Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology
Thomas Hesterkamp: German Center for Infection Research, Translational Project Management Office
Christian Drosten: Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology
Felix F. Loeffler: Max Planck Institute of Colloids and Interfaces, Department of Biomolecular Systems
Bart L. Haagmans: Erasmus Medical Center, Department of Viroscience
Gerd Sutter: LMU University of Munich, Institute of Infectious Diseases and Zoonoses
Stephan Becker: Philipps University Marburg, Institute of Virology
Marylyn M. Addo: University Medical Center Hamburg-Eppendorf, Institute for Infection Research and Vaccine Development (IIRVD)

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Vaccine development is essential for pandemic preparedness. We previously conducted a Phase 1 clinical trial of the vector vaccine candidate MVA-MERS-S against the Middle East respiratory syndrome coronavirus (MERS-CoV), expressing its full spike glycoprotein (MERS-CoV-S), as a homologous two-dose regimen (Days 0 and 28). Here, we evaluate the safety (primary objective) and immunogenicity (secondary and exploratory objectives: magnitude and characterization of vaccine-induced humoral responses) of a third vaccination with MVA-MERS-S in a subgroup of trial participants one year after primary immunization. MVA-MERS-S booster vaccination is safe and well-tolerated. Both binding and neutralizing anti-MERS-CoV antibody titers increase substantially in all participants and exceed maximum titers observed after primary immunization more than 10-fold. We identify four immunogenic IgG epitopes, located in the receptor-binding domain (RBD, n = 1) and the S2 subunit (n = 3) of MERS-CoV-S. The level of baseline anti-human coronavirus antibody titers does not impact the generation of anti-MERS-CoV antibody responses. Our data support the rationale of a booster vaccination with MVA-MERS-S and encourage further investigation in larger trials. Trial registration: Clinicaltrials.gov NCT03615911.

Date: 2022
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DOI: 10.1038/s41467-022-31557-0

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