tetano
Editor, Senior Moderator
J Gen Virol
. 2025 Nov;106(11):002180.
doi: 10.1099/jgv.0.002180. Strong immunogenicity and protection against SARS-CoV-2 in hamsters induced by heterologous boost vaccination with an MVA-based COVID-19 vaccine candidate
Sonja Ohrnberger[SUP] 1 [/SUP], Christian Meyer Zu Natrup[SUP] 1 [/SUP], Sabrina Clever[SUP] 1 [/SUP], Lisa-Marie Schünemann[SUP] 1 [/SUP], Federico Armando[SUP] 2 [/SUP], Malgorzata Ciurkiewicz[SUP] 2 [/SUP], Wolfgang Baumgärtner[SUP] 2 [/SUP], Georgia Kalodimou[SUP] 3 [/SUP], Gerd Sutter[SUP] 3 [/SUP], Alina Tscherne[SUP] 3 [/SUP], Asisa Volz[SUP] 1 [/SUP]
Affiliations
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.
Keywords: emerging viruses; heterologous vaccination; low-dose vaccination; modified vaccinia virus Ankara; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
. 2025 Nov;106(11):002180.
doi: 10.1099/jgv.0.002180. Strong immunogenicity and protection against SARS-CoV-2 in hamsters induced by heterologous boost vaccination with an MVA-based COVID-19 vaccine candidate
Sonja Ohrnberger[SUP] 1 [/SUP], Christian Meyer Zu Natrup[SUP] 1 [/SUP], Sabrina Clever[SUP] 1 [/SUP], Lisa-Marie Schünemann[SUP] 1 [/SUP], Federico Armando[SUP] 2 [/SUP], Malgorzata Ciurkiewicz[SUP] 2 [/SUP], Wolfgang Baumgärtner[SUP] 2 [/SUP], Georgia Kalodimou[SUP] 3 [/SUP], Gerd Sutter[SUP] 3 [/SUP], Alina Tscherne[SUP] 3 [/SUP], Asisa Volz[SUP] 1 [/SUP]
Affiliations
- PMID: 41258789
- PMCID: PMC12629099
- DOI: 10.1099/jgv.0.002180
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.
Keywords: emerging viruses; heterologous vaccination; low-dose vaccination; modified vaccinia virus Ankara; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).