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.
【저자키워드】 S protein, Dose-response, Neutralizing antibodies, 【초록키워드】 Vaccine, immune response, vaccination, immunogenicity, reactogenicity, severity, Local, ELISA, LNP, Lipid nanoparticles, Receptor binding domain, Protein, enzyme-linked immunosorbent assay, IgG antibody, IgG antibodies, Germany, RBD, immune responses, response, Mild, Placebo, group, Belgium, moderate, platform, convalescent sera, Lipid nanoparticle, SARS-CoV‑2, Frequency, Escalation, Munich, Safe, Phase 1, phase 1 study, CVnCoV, supplementary material, second dose, enzyme, dosage, interim analysis, CVnCoV doses, Dosage-dependent increases, Ghent, Hannover, SARS-CoV‑2 neutralizing titers, SARS-CoV‑2 S‑protein, sequence-optimized mRNA coding, serious AEs, systemic adverse events, S‑protein, Tübingen, CureVac, systemic AEs, Volunteer, enzyme-linked immunosorbent, Result, was measured, healthy, seroconverted, comparable, elicited, increases in, CVnCoV dose, CVnCoV vaccination, intramuscular dose, local AEs, overlapped, SARS-CoV‑2 neutralizing titer, systemic adverse event, 【제목키워드】 SARS-CoV-2, randomized clinical trial, Safety, vaccine candidate,