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

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, Marek Widera, Sandra Ciesek, Stefan O. Mueller, Thomas C. Mettenleiter, Domenico Maione, Benjamin Petsch, Martin Beer () and Anca Dorhoi ()
Additional contact information
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
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

Nature Communications, 2023, vol. 14, issue 1, 1-8

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36110-1

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