Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination

Alina Tscherne; Jan Hendrik Schwarz; Cornelius Rohde; Alexandra Kupke; Georgia Kalodimou; Leonard Limpinsel; Nisreen M.A. Okba; Berislav Bošnjak; Inga Sandrock; Ivan Odak; Sandro Halwe; Lucie Sauerhering; Katrin Brosinski; Nan Liangliang; Elke Duell; Sylvia Jany; Astrid Freudenstein; Jörg Schmidt; Anke Werner; Michelle Gellhorn Serra; Michael Klüver; Wolfgang Guggemos; Michael Seilmaier; Clemens Martin Wendtner; Reinhold Förster; Bart L. Haagmans; Stephan Becker; Gerd Sutter; Asisa Volz

doi:10.1073/pnas.2026207118

Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination

Alina Tscherne, Jan Hendrik Schwarz, Cornelius Rohde, Alexandra Kupke, Georgia Kalodimou, Leonard Limpinsel, Nisreen M.A. Okba, Berislav Bošnjak, Inga Sandrock, Ivan Odak, Sandro Halwe, Lucie Sauerhering, Katrin Brosinski, Nan Liangliang, Elke Duell, Sylvia Jany, Astrid Freudenstein, Jörg Schmidt, Anke Werner, Michelle Gellhorn SerraMichael Klüver, Wolfgang Guggemos, Michael Seilmaier, Clemens Martin Wendtner, Reinhold Förster, Bart L. Haagmans, Stephan Becker, Gerd Sutter^*, Asisa Volz

^*Corresponding author for this work

Virology

Research output: Contribution to journal › Article › Academic › peer-review

58 Citations (Scopus)

Abstract

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on modified vaccinia virus Ankara (MVA) against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here,we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust expression of S protein as antigen, make it a suitable candidate vaccine for industrial-scale production. Vaccinated mice produced S-specific CD8+ T cells and serum antibodies binding to S protein that neutralized SARS-CoV-2. Primeboost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.

Original language	English
Article number	e2026207118
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	118
Issue number	28
DOIs	https://doi.org/10.1073/pnas.2026207118
Publication status	Published - 13 Jul 2021

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. We thank Patrizia Bonert, Ursula Klostermeier, Johannes Döring, and Axel Groß for expert help in animal studies. We thank Nico Becker, Astrid Herwig, and Lennart Kämper for help with BSL3 sample preparation and testing. This work was supported by the German Center for Infection Research (Projects TTU 01.921 to G.S. and S.B.; TTU 01.712 to G.S.), the Federal Ministry of Education and Research (BMBF) (01KX2026 to G.S. and S.B.; BMBF 01KI20702 to G.S. and S.B.; ZOOVAC 01KI1718, RAPID 01KI1723G to A.V.; “NaFoUniMedCovid19” FKZ: 01KX2021, Project “B-FAST” to R.F. and S.B.). Deutsche Forschungsgemeinschaft (DFG) (German Research Foundation) Excellence Strategy EXC 2155 “RESIST” (Project ID39087428 to R.F.), by DFG Grant SFB900-B1 (Projektnummer 158989968 to R.F.), and by funds of the state of Lower Saxony (14-76103-184 CORONA-11/20 to R.F.).

Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.

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Tscherne, A., Hendrik Schwarz, J., Rohde, C., Kupke, A., Kalodimou, G., Limpinsel, L., Okba, N. M. A., Bošnjak, B., Sandrock, I., Odak, I., Halwe, S., Sauerhering, L., Brosinski, K., Liangliang, N., Duell, E., Jany, S., Freudenstein, A., Schmidt, J., Werner, A., ... Volz, A. (2021). Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination. Proceedings of the National Academy of Sciences of the United States of America, 118(28), Article e2026207118. https://doi.org/10.1073/pnas.2026207118

@article{6732bd069ccc410cadc1d4dee93692ec,

title = "Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination",

abstract = "Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on modified vaccinia virus Ankara (MVA) against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here,we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust expression of S protein as antigen, make it a suitable candidate vaccine for industrial-scale production. Vaccinated mice produced S-specific CD8+ T cells and serum antibodies binding to S protein that neutralized SARS-CoV-2. Primeboost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.",

author = "Alina Tscherne and {Hendrik Schwarz}, Jan and Cornelius Rohde and Alexandra Kupke and Georgia Kalodimou and Leonard Limpinsel and Okba, {Nisreen M.A.} and Berislav Bo{\v s}njak and Inga Sandrock and Ivan Odak and Sandro Halwe and Lucie Sauerhering and Katrin Brosinski and Nan Liangliang and Elke Duell and Sylvia Jany and Astrid Freudenstein and J{\"o}rg Schmidt and Anke Werner and Serra, {Michelle Gellhorn} and Michael Kl{\"u}ver and Wolfgang Guggemos and Michael Seilmaier and Wendtner, {Clemens Martin} and Reinhold F{\"o}rster and Haagmans, {Bart L.} and Stephan Becker and Gerd Sutter and Asisa Volz",

note = "Funding Information: ACKNOWLEDGMENTS. We thank Patrizia Bonert, Ursula Klostermeier, Johannes D{\"o}ring, and Axel Gro{\ss} for expert help in animal studies. We thank Nico Becker, Astrid Herwig, and Lennart K{\"a}mper for help with BSL3 sample preparation and testing. This work was supported by the German Center for Infection Research (Projects TTU 01.921 to G.S. and S.B.; TTU 01.712 to G.S.), the Federal Ministry of Education and Research (BMBF) (01KX2026 to G.S. and S.B.; BMBF 01KI20702 to G.S. and S.B.; ZOOVAC 01KI1718, RAPID 01KI1723G to A.V.; “NaFoUniMedCovid19” FKZ: 01KX2021, Project “B-FAST” to R.F. and S.B.). Deutsche Forschungsgemeinschaft (DFG) (German Research Foundation) Excellence Strategy EXC 2155 “RESIST” (Project ID39087428 to R.F.), by DFG Grant SFB900-B1 (Projektnummer 158989968 to R.F.), and by funds of the state of Lower Saxony (14-76103-184 CORONA-11/20 to R.F.). Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved.",

year = "2021",

month = jul,

day = "13",

doi = "10.1073/pnas.2026207118",

language = "English",

volume = "118",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "28",

}

Tscherne, A, Hendrik Schwarz, J, Rohde, C, Kupke, A, Kalodimou, G, Limpinsel, L, Okba, NMA, Bošnjak, B, Sandrock, I, Odak, I, Halwe, S, Sauerhering, L, Brosinski, K, Liangliang, N, Duell, E, Jany, S, Freudenstein, A, Schmidt, J, Werner, A, Serra, MG, Klüver, M, Guggemos, W, Seilmaier, M, Wendtner, CM, Förster, R, Haagmans, BL, Becker, S, Sutter, G & Volz, A 2021, 'Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 28, e2026207118. https://doi.org/10.1073/pnas.2026207118

Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination. / Tscherne, Alina; Hendrik Schwarz, Jan; Rohde, Cornelius et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 118, No. 28, e2026207118, 13.07.2021.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination

AU - Tscherne, Alina

AU - Hendrik Schwarz, Jan

AU - Rohde, Cornelius

AU - Kupke, Alexandra

AU - Kalodimou, Georgia

AU - Limpinsel, Leonard

AU - Okba, Nisreen M.A.

AU - Bošnjak, Berislav

AU - Sandrock, Inga

AU - Odak, Ivan

AU - Halwe, Sandro

AU - Sauerhering, Lucie

AU - Brosinski, Katrin

AU - Liangliang, Nan

AU - Duell, Elke

AU - Jany, Sylvia

AU - Freudenstein, Astrid

AU - Schmidt, Jörg

AU - Werner, Anke

AU - Serra, Michelle Gellhorn

AU - Klüver, Michael

AU - Guggemos, Wolfgang

AU - Seilmaier, Michael

AU - Wendtner, Clemens Martin

AU - Förster, Reinhold

AU - Haagmans, Bart L.

AU - Becker, Stephan

AU - Sutter, Gerd

AU - Volz, Asisa

N1 - Funding Information: ACKNOWLEDGMENTS. We thank Patrizia Bonert, Ursula Klostermeier, Johannes Döring, and Axel Groß for expert help in animal studies. We thank Nico Becker, Astrid Herwig, and Lennart Kämper for help with BSL3 sample preparation and testing. This work was supported by the German Center for Infection Research (Projects TTU 01.921 to G.S. and S.B.; TTU 01.712 to G.S.), the Federal Ministry of Education and Research (BMBF) (01KX2026 to G.S. and S.B.; BMBF 01KI20702 to G.S. and S.B.; ZOOVAC 01KI1718, RAPID 01KI1723G to A.V.; “NaFoUniMedCovid19” FKZ: 01KX2021, Project “B-FAST” to R.F. and S.B.). Deutsche Forschungsgemeinschaft (DFG) (German Research Foundation) Excellence Strategy EXC 2155 “RESIST” (Project ID39087428 to R.F.), by DFG Grant SFB900-B1 (Projektnummer 158989968 to R.F.), and by funds of the state of Lower Saxony (14-76103-184 CORONA-11/20 to R.F.). Publisher Copyright: © 2021 National Academy of Sciences. All rights reserved.

PY - 2021/7/13

Y1 - 2021/7/13

N2 - Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on modified vaccinia virus Ankara (MVA) against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here,we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust expression of S protein as antigen, make it a suitable candidate vaccine for industrial-scale production. Vaccinated mice produced S-specific CD8+ T cells and serum antibodies binding to S protein that neutralized SARS-CoV-2. Primeboost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.

AB - Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on modified vaccinia virus Ankara (MVA) against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here,we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust expression of S protein as antigen, make it a suitable candidate vaccine for industrial-scale production. Vaccinated mice produced S-specific CD8+ T cells and serum antibodies binding to S protein that neutralized SARS-CoV-2. Primeboost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.

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U2 - 10.1073/pnas.2026207118

DO - 10.1073/pnas.2026207118

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AN - SCOPUS:85109034703

SN - 0027-8424

VL - 118

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 28

M1 - e2026207118

ER -

Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination

Abstract

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