RT Journal Article
SR Electronic
T1 Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.20.485440
DO 10.1101/2022.04.20.485440
A1 Björn Corleis
A1 Donata Hoffmann
A1 Susanne Rauch
A1 Charlie Fricke
A1 Nicole Roth
A1 Janina Gergen
A1 Kristina Kovacikova
A1 Kore Schlottau
A1 Nico Joel Halwe
A1 Lorenz Ulrich
A1 Jacob Schön
A1 Kerstin Wernike
A1 Marek Widera
A1 Sandra Ciesek
A1 Stefan O. Mueller
A1 Thomas C. Mettenleiter
A1 Benjamin Petsch
A1 Martin Beer
A1 Anca Dorhoi
YR 2022
UL http://biorxiv.org/content/early/2022/04/20/2022.04.20.485440.abstract
AB 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.