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

Kremsner, Peter G.; Mann, Philipp; Kroidl, Arne; Leroux-Roels, Isabel; Schindler, Christoph; Gabor, Julian J.; Schunk, Mirjam; Leroux-Roels, Geert; Bosch, Jacobus J.; Fendel, Rolf; Kreidenweiss, Andrea; Velavan, Thirumalaisamy P.; Fotin-Mleczek, Mariola; Mueller, Stefan O.; Quintini, Gianluca; Schönborn‑Kellenberger, Oliver; Vahrenhorst, Dominik; Verstraeten, Thomas; Alves de Mesquita, Margarida; Walz, Lisa; Wolz, Olaf‑Oliver; Oostvogels, Lidia

BACKGROUND: We used the RNActive® technology platform (CureVac N.V., Tübingen, 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 Tübingen, 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 (MN(50)). RESULTS: In 245 volunteers who received 2 CVnCoV vaccinations (2 μg, n = 47, 4 μg, n = 48, 6 μg, n = 46, 8 μg, n = 44, 12 μg, 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 MN(50) 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 MN(50) in the 12 μg group. Responses to 12 μg 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 μg dosages elicited levels of immune responses that overlapped those observed in convalescent sera. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s00508-021-01922-y) contains supplementary material, which is available to authorized users.