TY - JOUR T1 - Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model JF - bioRxiv DO - 10.1101/2022.04.20.485440 SP - 2022.04.20.485440 AU - Björn Corleis AU - Donata Hoffmann AU - Susanne Rauch AU - Charlie Fricke AU - Nicole Roth AU - Janina Gergen AU - Kristina Kovacikova AU - Kore Schlottau AU - Nico Joel Halwe AU - Lorenz Ulrich AU - Jacob Schön AU - Kerstin Wernike AU - Marek Widera AU - Sandra Ciesek AU - Stefan O. Mueller AU - Thomas C. Mettenleiter AU - Benjamin Petsch AU - Martin Beer AU - Anca Dorhoi Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/04/20/2022.04.20.485440.abstract N2 - 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.Competing Interest StatementB Corleis, A Dorhoi, B Petsch and M Beer declare institutional funding for the work. SO Mueller and B Petsch declare holding company shares or stock options. The remaining authors declare no competing interests. ER -