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

Corleis, Björn;
GND
133501620
Hoffmann, Donata;
Zugehörigkeit
CureVac AG, Tübingen
Rauch, Susanne; Fricke, Charlie;
Zugehörigkeit
CureVac AG, Tübingen
Roth, Nicole;
Zugehörigkeit
CureVac AG, Tübingen
Gergen, Janina; Kovacikova, Kristina; Schlottau, Kore; Halwe, Nico; Ulrich, Lorenz; Schön, Jacob; Wernike, Kerstin; Widera, Marek; Ciesek, Sandra;
Zugehörigkeit
CureVac AG, Tübingen
Mueller, Stefan Otto;
GND
141505168
Mettenleiter, Thomas C.;
Zugehörigkeit
CureVac AG, Tübingen
Petsch, Benjamin; Beer, Martin; Dorhoi, Anca

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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