Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model

Corleis, B.; Hoffmann, D.; Rauch, S.; Fricke, C.; Roth, N.; Gergen, J.; Kovacikova, K.; Schlottau, K.; Halwe, N. J.; Ulrich, L.; Schön, J.; Wernike, K.; Widera, M.; Ciesek, S.; Mueller, S. O.; Mettenleiter, T. C.; Petsch, B.; Beer, M.; Dorhoi, A.

doi:10.1101/2022.04.20.485440

bioRxiv · 10.1101/2022.04.20.485440

Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model

Corleis, B.·Hoffmann, D.·Rauch, S.·Fricke, C.·Roth, N.·Gergen, J.·Kovacikova, K.·Schlottau, K.·Halwe, N. J.·Ulrich, L.·Schön, J.·Wernike, K.·Widera, M.·Ciesek, S.·Mueller, S. O.·Mettenleiter, T. C.·Petsch, B.·Beer, M.·Dorhoi, A.

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Abstract

Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS-CoV-2 variants could improve COVID-19 control. We compared monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S-protein, primarily in a transgenic mouse model and a Wistar rat model. The low-dose bivalent mRNA vaccine contained half the mRNA of each respective monovalent vaccine, but induced comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, specific CD4+ and CD8+ responses, and fully protected transgenic mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduced viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized Wistar rats also contained neutralizing antibodies against the B.1.1.529 (Omicron BA.1) variant. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins is a feasible approach for increasing the potency of vaccines against emerging and co-circulating SARS-CoV-2 variants.

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Corleis, B., Hoffmann, D., Rauch, S., Fricke, C., Roth, N., Gergen, J., Kovacikova, K., Schlottau, K., Halwe, N. J., Ulrich, L., Schön, J., Wernike, K., Widera, M., Ciesek, S., Mueller, S. O., Mettenleiter, T. C., Petsch, B., Beer, M., Dorhoi, A.. 2022-04-20. Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model. https://doi.org/10.1101/2022.04.20.485440

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