CVnCoV protects human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2

Hoffmann, D.; Corleis, B.; Rauch, S.; Roth, N.; Muehe, J.; Halwe, N. J.; Ulrich, L.; Fricke, C.; Schoen, J.; Kraft, A.; Breithaupt, A.; Wernike, K.; Michelitsch, A.; Sick, F.; Wylezich, C.; Mueller, S. O.; Mettenleiter, T. C.; Petsch, B.; Dorhoi, A.; Beer, M.

doi:10.1101/2021.03.22.435960

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bioRxiv · 10.1101/2021.03.22.435960

CVnCoV protects human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2

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Abstract

The ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic necessitates the fast development of vaccines as the primary control option. Recently, viral mutants termed "variants of concern" (VOC) have emerged with the potential to escape host immunity. VOC B.1.351 was first discovered in South Africa in late 2020, and causes global concern due to poor neutralization with propensity to evade preexisting immunity from ancestral strains. We tested the efficacy of a spike encoding mRNA vaccine (CVnCoV) against the ancestral strain BavPat1 and the novel VOC B.1.351 in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice developed elevated SARS-CoV-2 RBD-specific antibody as well as neutralization titers against the ancestral strain BavPat1. Neutralization titers against VOC B.1.351 were readily detectable but significantly reduced compared to BavPat1. VOC B.1.351-infected control animals experienced a delayed course of disease, yet nearly all SARS-CoV-2 challenged naive mice succumbed with virus dissemination and high viral loads. CVnCoV vaccine completely protected the animals from disease and mortality caused by either viral strain. Moreover, SARS-CoV-2 was not detected in oral swabs, lung, or brain in these groups. Only partial protection was observed in mice receiving the formalin-inactivated virus preparation. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV shows complete disease protection against the novel VOC B.1.351 in our studies.

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Hoffmann, D., Corleis, B., Rauch, S., Roth, N., Muehe, J., Halwe, N. J., Ulrich, L., Fricke, C., Schoen, J., Kraft, A., Breithaupt, A., Wernike, K., Michelitsch, A., Sick, F., Wylezich, C., Mueller, S. O., Mettenleiter, T. C., Petsch, B., Dorhoi, A., Beer, M.. 2021-03-22. CVnCoV protects human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2. https://doi.org/10.1101/2021.03.22.435960

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