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Summary 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 (MN50). 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 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 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.

Recent findings indicate that the kinetics of B-cell reconstitution after marrow transplantation mimic normal ontogeny. The early B-cell repertoire during ontogeny is characterized by a high degree of autoreactivity and interconnectivity. Therefore, in a prospective analysis, 95 consecutive recipients of an allogeneic marrow transplant were screened for the occurrence of various autoantibodies and 47 of these 95 were also screened for monoclonal gammopathies. None of the patients developed antibodies specific for systemic autoimmune disorders. In contrast, a high prevalence of natural antibodies (79/95) was found early post-transplant, with 58 of these 79 patients developing two or more autoantibodies. According to multiple regression, the mean number of natural antibodies (95% confidence limits in parentheses) depends significantly (P = 0.006) on the status of CMV infection: 0.9 (0.4; 1.6) CMV-negative: 2.0 (1.0; 3.3) asymptomatic CMV infection; 3.1 (1.7; 5.0) CMV disease. Sex, age, underlying disease, conditioning therapy, acute graft-versus-host disease and CMV serology of donor and recipient pretransplant did not affect the number of natural autoantibodies. Monoclonal gammopathies were detected in 12/47 patients with a predominance of the IgG-kappa subtype. All these 12 patients suffered from a viral infection (CMV, n = 11: influenza strain A, n = 1). The high degree of self-reactivity post-transplant further supports the hypothesis that B-cell reconstitution mimics ontogeny. Moreover, these data indicate nonspecific polyclonal, CMV-mediated, presumably T-cell independent B-cell stimulation and disturbed T-cell regulatory function following allogeneic BMT.

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