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.

@article{fathi2026safety,
  title = {{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.}},
  author = {Anahita Fathi and Christine Dahlke and Leonie Mayer and Sibylle C Mellinghoff and Verena Krähling and Sandro Halwe and Helena Müller-Kräuter and Rolf Fendel and Peter Kremsner and Meral Esen and Martha Klug and Marc Lütgehetmann and Leonie M Weskamm and MVA-SARS-2-S Study Group and Gerd Sutter and Stephan Becker and Svenja Hardtke and Marylyn M Addo},
  journal = {Human vaccines \& immunotherapeutics},
  year = {2026},
  month = oct,
  doi = {10.1080/21645515.2026.2728535},
  url = {https://europepmc.org/article/MED/42878689},
  note = {CC BY-NC},
}

TY  - JOUR
TI  - 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.
AU  - Anahita Fathi
AU  - Christine Dahlke
AU  - Leonie Mayer
AU  - Sibylle C Mellinghoff
AU  - Verena Krähling
AU  - Sandro Halwe
AU  - Helena Müller-Kräuter
AU  - Rolf Fendel
AU  - Peter Kremsner
AU  - Meral Esen
AU  - Martha Klug
AU  - Marc Lütgehetmann
AU  - Leonie M Weskamm
AU  - MVA-SARS-2-S Study Group
AU  - Gerd Sutter
AU  - Stephan Becker
AU  - Svenja Hardtke
AU  - Marylyn M Addo
PY  - 2026
DA  - 2026/10/15
JO  - Human vaccines & immunotherapeutics
DO  - 10.1080/21645515.2026.2728535
UR  - https://europepmc.org/article/MED/42878689
AB  - 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.
SN  - 2164-5515
SN  - 2164-554X
ER  -