Journal Article

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

Paris, Grigori, Dahlke, Christine, Okba, Nisreen M. A., Corman, Victor M., Müller, Marcel A., Hesterkamp, Thomas, Tscherne, Alina, Becker, Stephan, Ly, My L., Fathi, Anahita, Friedrich, Monika, Fux, Robert, Krähling, Verena, Schmiedel, Stefan, Drosten, Christian, Kalodimou, Georgia, Addo, Marylyn M., Lassen, Susan, Sutter, Gerd, Raadsen, Matthijs P., Heidepriem, Jasmin, Kupke, Alexandra, Klüver, Michael, Loeffler, Felix F., Haagmans, Bart L., Volz, Asisa, Koch, Till

2022

Overview

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. In a clinical trial, Fathi et al. show that a booster vaccination with a vector vaccine candidate against the highly pathogenic Middle East Respiratory Syndrome coronavirus is safe and strongly improves the immunity generated by primary immunization.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 631/250/2152/2153/1291 / 631/250/590 / Antibodies / Antibodies, Neutralizing / Antibodies, Viral / Binding / Clinical trials / Coronavirus Infections / Coronaviruses / COVID-19 / Epitopes / Glycoproteins / Homology / Humanities and Social Sciences / Humans / Immunization / Immunogenicity / Immunoglobulin G / Middle East respiratory syndrome / Middle East Respiratory Syndrome Coronavirus / multidisciplinary / Neutralization / Pandemics / Respiratory diseases / Science / Science (multidisciplinary) / Spike glycoprotein / Spike Glycoprotein, Coronavirus / Subgroups / Vaccination / Vaccine development / Vaccines / Viral Vaccines