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Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models

Author

Listed:
  • Björn Corleis

    (Friedrich-Loeffler-Institut)

  • Donata Hoffmann

    (Friedrich-Loeffler-Institut)

  • Susanne Rauch

    (CureVac SE)

  • Charlie Fricke

    (Friedrich-Loeffler-Institut)

  • Nicole Roth

    (CureVac SE)

  • Janina Gergen

    (CureVac SE)

  • Kristina Kovacikova

    (CureVac SE)

  • Kore Schlottau

    (Friedrich-Loeffler-Institut)

  • Nico Joel Halwe

    (Friedrich-Loeffler-Institut)

  • Lorenz Ulrich

    (Friedrich-Loeffler-Institut)

  • Jacob Schön

    (Friedrich-Loeffler-Institut)

  • Kerstin Wernike

    (Friedrich-Loeffler-Institut)

  • Marek Widera

    (University Hospital Frankfurt, Goethe University Frankfurt)

  • Sandra Ciesek

    (University Hospital Frankfurt, Goethe University Frankfurt
    German Center for Infection Research (DZIF)
    Fraunhofer Institute for Molecular Biology and Applied Ecology (IME))

  • Stefan O. Mueller

    (CureVac SE)

  • Thomas C. Mettenleiter

    (Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health)

  • Domenico Maione

    (GSK)

  • Benjamin Petsch

    (CureVac SE)

  • Martin Beer

    (Friedrich-Loeffler-Institut)

  • Anca Dorhoi

    (Friedrich-Loeffler-Institut)

Abstract

Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS-CoV-2 variants could improve control of the COVID-19 pandemic. We compare monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S-protein in a transgenic mouse and a Wistar rat model. The blended low-dose bivalent mRNA vaccine contains half the mRNA of each respective monovalent vaccine, but induces comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, antigen-specific CD4+ and CD8+ responses, and protects transgenic female mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduces viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized female Wistar rats also contain neutralizing antibodies against the B.1.1.529 (Omicron BA.1 and BA.5) variants. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins are feasible approaches for extending the coverage of vaccines for emerging and co-circulating SARS-CoV-2 variants.

Suggested Citation

  • Björn Corleis & Donata Hoffmann & Susanne Rauch & Charlie Fricke & Nicole Roth & Janina Gergen & Kristina Kovacikova & Kore Schlottau & Nico Joel Halwe & Lorenz Ulrich & Jacob Schön & Kerstin Wernike , 2023. "Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36110-1
    DOI: 10.1038/s41467-023-36110-1
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