CVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2

Donata Hoffmann,Bernd Hoffmann,Janine Mühe,Björn Corleis,Jacob Schön,Nicole Roth,Benjamin Petsch,Nico Joel Halwe,Martin Beer,Franziska Sick,Kerstin Wernike,Susanne Rauch,Anna Michelitsch,Anna Kraft,Moritz Thran,Thomas C Mettenleiter,Claudia Wylezich,Lisa K Ulrich ,Angele Breithaupt,Stefan O Mueller,Charlie Fricke,Andreas Theß ,Anca Dorhoi

doi:10.1038/s41467-021-24339-7

Donata Hoffmann, Bernd Hoffmann + Show 21 more

Open Access

https://doi.org/10.1038/s41467-021-24339-7

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Abstract

The ongoing SARS-CoV-2 pandemic necessitates the fast development of vaccines. Recently, viral mutants termed variants of concern (VOC) which may escape host immunity have emerged. The efficacy of spike encoding mRNA vaccines (CVnCoV and CV2CoV) against the ancestral strain and the VOC B.1.351 was tested in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with a formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice develop elevated SARS-CoV-2 RBD-specific antibody and neutralization titers which are readily detectable, but significantly reduced against VOC B.1.351. The mRNA vaccines fully protect from disease and mortality caused by either viral strain. SARS-CoV-2 remains undetected in swabs, lung, or brain in these groups. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV and CV2CoV show complete disease protection against the novel VOC B.1.351 in our studies.

Highlights

The ongoing SARS-CoV-2 pandemic necessitates the fast development of vaccines
Several vaccines based on mRNA technology or viral vectors are authorized for emergency use and further products are in final licensing phases[3]
We investigated the efficacy of mRNA vaccines CVnCoV and CV2CoV against SARSCoV-2 using an early B lineage 614G strain and the novel variants of concern (VOC) B1.351 in a human ACE2 transgenic mouse model of severe COVID-1920

Summary

Introduction

The ongoing SARS-CoV-2 pandemic necessitates the fast development of vaccines. Recently, viral mutants termed variants of concern (VOC) which may escape host immunity have emerged. Viral evolution is a highly dynamic process that results in emergence of multiple, geographically distinct new variants, first identified in the UK (B1.1.7), South Africa (B.1.351), and Brazil (B.1.1.28; P1) (https://www.ecdc.europa.eu/en/publications-data/covid-19-riskassessment-variants-vaccine-fourteenth-update-february-2021). These variants of concern (VOCs) acquired numerous mutations, in the spike protein encoding gene (S), most frequently within the S1 and the receptor-binding domain (RBD)[7,8,9]. We investigated the efficacy of mRNA vaccines CVnCoV and CV2CoV against SARSCoV-2 using an early B lineage 614G strain and the novel VOC B1.351 in a human ACE2 (hACE2) transgenic mouse model of severe COVID-1920. The choice for the variant B.1.351 was related to the observed immune-escape features with a reduced neutralization efficacy[10] and decreased protective efficacy reported for a licensed vaccine[21]

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