CV 2 CoV , an enhanced mRNA based SARS-CoV-2 vaccine candidate 1 supports higher protein expression and improved immunogenicity in rats 2 3

More than a year after the start of the SARS-CoV-2 pandemic, multiple first generation vaccines are 14 approved and available for vaccination. Still, many challenges remain. The ongoing vaccination 15 programs across the globe suffer from insufficient vaccine supply. The virus is adapting to the human 16 host and more transmissible variants are circulating that are neutralised less efficiently by antibodies 17 raised against ancestral virus. Here we describe CV2CoV, a second generation mRNA vaccine 18 developed for enhanced protein expression and immunogenicity. CV2CoV supports increased levels 19 of protein expression in cell culture compared to our clinical candidate CVnCoV. Vaccination with 20 CV2CoV induces high levels of virus neutralising antibodies with accelerated kinetics in rats. Robust 21 antibody responses are reflected in significant cross-neutralisation of circulating SARS-CoV-2 variants 22 of concern, i.e. B.1.1.7 and B.1.351. Together, these results underline the value of CV2CoV as next 23 generation SARS-CoV-2 mRNA vaccine. 24 25 Introduction 26