Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2 : a phase 1 randomized clinical trial

Background We used the RNActive (R) technology platform (CureVac N.V., Tubingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilized form of SARS-CoV-2 spike (S) protein encapsulated in lipid nanoparticles (LNP). Methods This is an interim analysis of a dosage escalation phase 1 study in healthy 18-60-year-old volunteers in Hannover, Munich and Tubingen, Germany, and Ghent, Belgium. After giving 2 intramuscular doses of CVnCoV or placebo 28 days apart we assessed solicited local and systemic adverse events (AE) for 7 days and unsolicited AEs for 28 days after each vaccination. Immunogenicity was measured as enzyme-linked immunosorbent assay (ELISA) IgG antibodies to SARS-CoV-2 S-protein and receptor binding domain (RBD), and SARS-CoV-2 neutralizing titers (MN50). Results In 245 volunteers who received 2 CVnCoV vaccinations (2 mu g, n = 47, 4 mu g, n = 48, 6 mu g, n = 46, 8 mu g, n = 44, 12 mu g, n = 28) or placebo (n = 32) there were no vaccine-related serious AEs. Dosage-dependent increases in frequency and severity of solicited systemic AEs, and to a lesser extent local AEs, were mainly mild or moderate and transient in duration. Dosage-dependent increases in IgG antibodies to S-protein and RBD and MN50 were evident in all groups 2 weeks after the second dose when 100% (23/23) seroconverted to S-protein or RBD, and 83% (19/23) seroconverted for MN50 in the 12 mu g group. Responses to 12 mu g were comparable to those observed in convalescent sera from known COVID-19 patients. Conclusion In this study 2 CVnCoV doses were safe, with acceptable reactogenicity and 12 mu g dosages elicited levels of immune responses that overlapped those observed in convalescent sera