Safety and immunogenicity of a first-generation modified vaccinia virus Ankara-vectored SARS-CoV-2 vaccine candidate with mRNA-based booster vaccination: A phase 1 trial

The rapid development of effective COVID-19 vaccines was enabled by the parallel assessment of multiple candidates early in the pandemic, including candidates based on the Modified Vaccinia virus Ankara (MVA) vector platform. This Phase 1 trial (NCT04569383) evaluated the MVA-based vaccine candidate MVA-SARS-2-S, expressing the full-length native SARS-CoV-2 spike glycoprotein (Wuhan-HU-1). Between October 2020 and May 2021, 30 healthy, SARS-CoV-2–naive adults received two doses of either 107 or 108 international units (IU) of MVA-SARS-2-S 28 days apart, with 6-month follow-up. A subgroup (n = 12) received two BNT162b2 booster vaccinations. Safety and reactogenicity were primary objectives; secondary and exploratory objectives included S1 seroconversion rates, S-domain-specific antibodies, SARS-CoV-2-neutralizing antibodies, and spike-specific T cell responses. MVA-SARS-2-S demonstrated a good safety profile. No severe or serious adverse events occurred. Immunogenicity was poor: S1-specific seroconversion occurred in 0/15 (107 IU group) and 3/15 (108 IU group) participants. Binding antibodies were predominantly directed against the S2 subunit, with peak median anti-S2 fold changes of 6.0 and 5.2 in the 107 IU and 108 IU groups, respectively. Neutralizing antibodies were detected in one participant (108 IU group); spike-specific T cell responses were observed in 5/15 (107 IU group) and 2/13 (108 IU group) participants. Heterologous BNT162b2 vaccination induced S1 seroconversion and detectable neutralizing antibody and T cell responses in all boosted participants, without safety concerns. In conclusion, while MVA-SARS-2-S was well tolerated and did not adversely affect subsequent BNT162b2 boosting, the vaccine candidate elicited insufficient immunogenicity, underscoring the need for optimized antigen design.

Authors

Institutions

Publication Details

Journal
Human Vaccines & Immunotherapeutics
Published
2026-10-15
DOI
https://doi.org/10.1080/21645515.2026.2728535
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Safety and immunogenicity of a first-generation modified vaccinia virus Ankara-vectored SARS-CoV-2 vaccine candidate with mRNA-based booster vaccination: A phase 1 trial

Verena Krähling, Helena Müller-Kräuter, Gerd Sutter, Nicole Schneiderhan‐Marra et al.
Human Vaccines & Immunotherapeutics
SARS-CoV-2 and COVID-19 Research
article

Safety and immunogenicity of a first-generation modified vaccinia virus Ankara-vectored SARS-CoV-2 vaccine candidate with mRNA-based booster vaccination: A phase 1 trial

Verena Krähling, Helena Müller-Kräuter, Gerd Sutter, Nicole Schneiderhan‐Marra, Flaminia Olearo, Cordula Grüttner, Leonie Marie Weskamm, Anahita Fathi, Sandro Halwe, Leonie Mayer, Peter G. Kremsner, Niclas Renevier, Martha Klug, Stefanie K. Gräfe, Dominik Sebastian Nörz, My Linh Ly, Christine Dahlke, Monika Rottstegge, Stefan Schmiedel, Svenja Hardtke, Stephan W. Becker, Claudia Schlesner, Alex Dulovic, Rolf Fendel, Monika Friedrich, Sibylle C. Mellinghoff, Jana Kochmann, Meral Esen, Thomas Hesterkamp, Marylyn M. Addo, Marc Lütgehetmann, Maren Sandkuhl, Marie-Louise Dieck, MVA-SARS-2-S Study Group, Amelie Alberti, Yashin Simsek
article en

Abstract

The rapid development of effective COVID-19 vaccines was enabled by the parallel assessment of multiple candidates early in the pandemic, including candidates based on the Modified Vaccinia virus Ankara (MVA) vector platform. This Phase 1 trial (NCT04569383) evaluated the MVA-based vaccine candidate MVA-SARS-2-S, expressing the full-length native SARS-CoV-2 spike glycoprotein (Wuhan-HU-1). Between October 2020 and May 2021, 30 healthy, SARS-CoV-2–naive adults received two doses of either 107 or 108 international units (IU) of MVA-SARS-2-S 28 days apart, with 6-month follow-up. A subgroup (n = 12) received two BNT162b2 booster vaccinations. Safety and reactogenicity were primary objectives; secondary and exploratory objectives included S1 seroconversion rates, S-domain-specific antibodies, SARS-CoV-2-neutralizing antibodies, and spike-specific T cell responses. MVA-SARS-2-S demonstrated a good safety profile. No severe or serious adverse events occurred. Immunogenicity was poor: S1-specific seroconversion occurred in 0/15 (107 IU group) and 3/15 (108 IU group) participants. Binding antibodies were predominantly directed against the S2 subunit, with peak median anti-S2 fold changes of 6.0 and 5.2 in the 107 IU and 108 IU groups, respectively. Neutralizing antibodies were detected in one participant (108 IU group); spike-specific T cell responses were observed in 5/15 (107 IU group) and 2/13 (108 IU group) participants. Heterologous BNT162b2 vaccination induced S1 seroconversion and detectable neutralizing antibody and T cell responses in all boosted participants, without safety concerns. In conclusion, while MVA-SARS-2-S was well tolerated and did not adversely affect subsequent BNT162b2 boosting, the vaccine candidate elicited insufficient immunogenicity, underscoring the need for optimized antigen design.

Human Vaccines & ImmunotherapeuticsVol. 22(1)
Universität Hamburg (DE), Philipps University of Marburg (DE), Health First (US), Integrated Oncology (United States) (US), Centre de Recherche Médicales de Lambaréné (GA), University Medical Center Hamburg-Eppendorf (DE), Natural and Medical Sciences Institute (DE), German Center for Infection Research (DE), Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE), Institute of Medical Microbiology and Hygiene (DE), University of Tübingen (DE), Ludwig-Maximilians-Universität München (DE), Bernhard Nocht Institute for Tropical Medicine (DE)
Deutsches Zentrum für Infektionsforschung, Deutsche Forschungsgemeinschaft
Good health and well-being
Openalex Percentile: Top 12%
SARS-CoV-2 and COVID-19 Research
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.