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Journal of General Virology header logo Journal of General Virology

Volume 106, Issue 11

Strong immunogenicity and protection against SARS-CoV-2 in hamsters induced by heterologous boost vaccination with an MVA-based COVID-19 vaccine candidate Open Access

Abstract

Over the last decade, heterologous prime–boost vaccination regimens have been established as a promising strategy to enhance immune responses and make optimal use of the advantages of different vaccine platforms. Modified vaccinia virus Ankara (MVA), a replication-deficient poxviral vector with an established safety profile, is under clinical investigation as a versatile recombinant vaccine platform against various infectious diseases. In the context of coronavirus disease 2019 (COVID-19), a recombinant MVA-based vaccine candidate expressing the prefusion-stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (MVA-ST) has demonstrated safety, immunogenicity and protection in preclinical studies using different animal models. Furthermore, a phase Ib clinical trial in healthy adults showed that MVA-ST is safe, well-tolerated and immunogenic when used as a booster following mRNA priming. In this study, we evaluated heterologous prime–boost vaccination regimens using MVA-ST as a booster in Syrian hamsters. Hamsters were primed with an mRNA vaccine (BNT162b2, BioNTech/Pfizer) or the adenoviral vector vaccine Ad26.COV2.S (Janssen) and subsequently boosted with MVA-ST at a dose of 10⁸ p.f.u. These heterologous vaccination regimens induced robust protection against severe SARS-CoV-2 disease, with superior immunogenicity compared to homologous MVA-ST vaccination. Notably, even a lower booster dose (10⁷ p.f.u.) of MVA-ST following mRNA priming conferred strong protection against SARS-CoV-2 challenge infection, while still associated with limited viral shedding from the upper respiratory tract. These findings highlight the potential of MVA-ST as a heterologous booster to enhance the immunogenicity and protective efficacy of existing COVID-19 vaccines and also to improve vaccination strategies against other emerging pathogens.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): emerging viruses , heterologous vaccination , low-dose vaccination , modified vaccinia virus Ankara and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Funding
This study was supported by the:
  • Deutsche Forschungsgemeinschaft (Award 398066876/ GRK 2485/1)
    • Principal Award Recipient: AsisaVolz
  • Niedersächsische Ministerium für Wissenschaft und Kultur (Award 14 - 76103-184 CORONA-15/20)
    • Principal Award Recipient: AsisaVolz
  • Deutsches Zentrum für Infektionsforschung (Award DZIF FF 01.904)
    • Principal Award Recipient: AsisaVolz
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2025-11-19
2025-12-16

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Strong immunogenicity and protection against SARS-CoV-2 in hamsters induced by heterologous boost vaccination with an MVA-based COVID-19 vaccine candidate
J. Gen. Virol. 106, 002180 (2025); https://doi.org/10.1099/jgv.0.002180
/content/journal/jgv/10.1099/jgv.0.002180
/content/journal/jgv/10.1099/jgv.0.002180
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