Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2
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Abstract
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.
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SciScore for 10.1101/2020.11.09.20228551: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study protocol was approved by the appropriate Investigational Review Boards (IRB) and national regulatory authority for each site, and was registered with ClinicalTrials.gov (Identifier: NCT 04449276).
Consent: All participants provided written informed consent at enrollment.Randomization After assessing safety data for 60 hours, the iSRC and DSMB approved the vaccination of the remaining participants of that dosage group (including placebo subjects and subjects known to be seropositive for SARS-CoV-2, randomized and blinded) and the sentinels of the next higher dosage group. Blinding The first-in-human, placebo-controlled, blinded phase 1 trial of … SciScore for 10.1101/2020.11.09.20228551: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study protocol was approved by the appropriate Investigational Review Boards (IRB) and national regulatory authority for each site, and was registered with ClinicalTrials.gov (Identifier: NCT 04449276).
Consent: All participants provided written informed consent at enrollment.Randomization After assessing safety data for 60 hours, the iSRC and DSMB approved the vaccination of the remaining participants of that dosage group (including placebo subjects and subjects known to be seropositive for SARS-CoV-2, randomized and blinded) and the sentinels of the next higher dosage group. Blinding The first-in-human, placebo-controlled, blinded phase 1 trial of CVnCoV enrolled healthy adults (18 to 60 years). Power Analysis not detected. Sex as a biological variable Also excluded were active smokers within the previous year, pregnant or breastfeeding women, study sponsors, and study staff employees or relatives. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The main secondary objectives were the evaluation of the humoral immune response measured by SARS-CoV-2-S protein-specific IgG and RBD IgG (ELISA) antibodies, as well as SARS-CoV-2 virus neutralizing antibodies. RBD IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Afterwards, semi-confluent Vero E6 cells (ATCC, Cat.1586) were incubated with the virus - serum mixtures at 37°C 5% CO2 for 3 days. Vero E6suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04449276 Active, not recruiting A Study to Evaluate the Safety, Reactogenicity and Immunogen… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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