PT  - JOURNAL ARTICLE
AU  - Susanne Rauch
AU  - Nicole Roth
AU  - Kim Schwendt
AU  - Mariola Fotin-Mleczek
AU  - Stefan O. Mueller
AU  - Benjamin Petsch
TI  - mRNA based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus neutralizing antibodies and mediates protection in rodents
AID  - 10.1101/2020.10.23.351775
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.23.351775
4099  - http://biorxiv.org/content/early/2020/10/23/2020.10.23.351775.short
4100  - http://biorxiv.org/content/early/2020/10/23/2020.10.23.351775.full
AB  - The devastating SARS-CoV-2 pandemic demands rapid vaccine development and large scale production to meet worldwide needs. mRNA vaccines have emerged as one of the most promising technologies to address this unprecedented challenge. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle (LNP) encapsulated non-modified mRNA vaccine that encodes the full length, pre-fusion stabilised SARS-CoV-2 Spike (S) protein. S translated from CVnCoV is cleaved, post-translationally modified, and presented on the cell surface, highlighting the ability of mRNA vaccines to mimic antigen presentation during viral infection. Immunisation with CVnCoV induced strong humoral responses with high titres of virus neutralizing antibodies in mice and hamsters and robust CD4+ and CD8+ T cell responses in mice. Most importantly, vaccination with CVnCoV fully protected hamster lungs from challenge with wild type SARS-CoV-2. To gain insights in the risk of vaccine-enhanced disease, hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication were analysed for signs of vaccine-enhanced disease. No evidence of increased viral replication or exacerbated inflammation and damage to viral target organs was detectable, giving strong evidence for a favourable safety profile of CVnCoV. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.Competing Interest StatementM.F-M. is a management board member and employee of CureVac AG, Tuebingen Germany. S.R., B.P., N.R., K.S. and S.O.M. are employees of CureVac AG, Tuebingen Germany, a publically listed company developing RNA-based vaccines and immunotherapeutics. All authors may hold shares or stock options in the company. S.R., B.P., N.R., K.S., M.F-M. inventors on several patents on mRNA vaccination and use thereof.