tetano
Editor, Senior Moderator
Hum Vaccin Immunother
. 2026 Dec;22(1):2728535.
doi: 10.1080/21645515.2026.2728535. Epub 2026 Oct 15.
Anahita Fathi 1 2 3 4 , Christine Dahlke 1 2 3 , Leonie Mayer 1 2 3 , Sibylle C Mellinghoff 1 2 5 6 7 , Verena Krähling 8 9 , Sandro Halwe 8 9 , Helena Müller-Kräuter 9 , Rolf Fendel 10 11 12 , Peter Kremsner 10 11 12 , Meral Esen 10 11 12 , Martha Klug 10 11 , Marc Lütgehetmann 3 13 , Leonie M Weskamm 1 2 3 ; MVA-SARS-2-S Study Group; Gerd Sutter 14 15 , Stephan Becker 8 9 , Svenja Hardtke 1 2 3 , Marylyn M Addo 1 2 3
Collaborators, Affiliations Expand
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.
Keywords: BNT162b2; MVA-SARS-2-S; SARS-CoV-2; coronavirus vaccine; modified vaccinia virus ankara; vector vaccine.
. 2026 Dec;22(1):2728535.
doi: 10.1080/21645515.2026.2728535. Epub 2026 Oct 15.
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
Anahita Fathi 1 2 3 4 , Christine Dahlke 1 2 3 , Leonie Mayer 1 2 3 , Sibylle C Mellinghoff 1 2 5 6 7 , Verena Krähling 8 9 , Sandro Halwe 8 9 , Helena Müller-Kräuter 9 , Rolf Fendel 10 11 12 , Peter Kremsner 10 11 12 , Meral Esen 10 11 12 , Martha Klug 10 11 , Marc Lütgehetmann 3 13 , Leonie M Weskamm 1 2 3 ; MVA-SARS-2-S Study Group; Gerd Sutter 14 15 , Stephan Becker 8 9 , Svenja Hardtke 1 2 3 , Marylyn M Addo 1 2 3
Collaborators, Affiliations Expand
- PMID: 42878689
- DOI: 10.1080/21645515.2026.2728535
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.
Keywords: BNT162b2; MVA-SARS-2-S; SARS-CoV-2; coronavirus vaccine; modified vaccinia virus ankara; vector vaccine.