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

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.

No Evidence for the Presence of SARS-CoV-2 in Bank Voles and Other Rodents in Germany, 2020–2022

“…In conclusion, we found no evidence for the presence of SARS-CoV-2 in the surveilled wild rodent populations using serological test systems that have been demonstrated to detect antibodies against diverse VOCs of SARS-CoV-2 [ 35 , 36 ]. Nevertheless, rodents should be included in future monitoring studies, especially in regions with high human population densities and where the beta and gamma variants are more prevalent, and when new virus variants emerge during the continued evolution of SARS-CoV-2 and when the potential of the variants to break cross-species barriers and the capability to expand species tropism to animals is unknown.…”

“…As positive controls, blood samples collected on day 8 (two animals), 12 (one animal) or 21 (three animals) after experimental SARS-CoV-2 inoculation of bank voles [ 19 ] have been tested, the results are shown in Figure 1 . The suitability of the ELISA to detect antibodies directed against diverse VOCs has been shown during experimental infection studies [ 35 , 36 ].…”