Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2 : A phase 1 randomized clinical trial
© 2021. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:133 |
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| Enthalten in: |
Wiener klinische Wochenschrift - 133(2021), 17-18 vom: 11. Sept., Seite 931-941 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kremsner, Peter G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.09.2021 Date Revised 02.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00508-021-01922-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Kremsner, Peter G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2 |b A phase 1 randomized clinical trial |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 17.09.2021 | ||
| 500 | |a Date Revised 02.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s). | ||
| 520 | |a 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) | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Dose-response | |
| 650 | 4 | |a Neutralizing antibodies | |
| 650 | 4 | |a Reactogenicity | |
| 650 | 4 | |a S protein | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a COVID-19 Vaccines |2 NLM | |
| 650 | 7 | |a Lipids |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Vaccines |2 NLM | |
| 700 | 1 | |a Mann, Philipp |e verfasserin |4 aut | |
| 700 | 1 | |a Kroidl, Arne |e verfasserin |4 aut | |
| 700 | 1 | |a Leroux-Roels, Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Schindler, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Gabor, Julian J |e verfasserin |4 aut | |
| 700 | 1 | |a Schunk, Mirjam |e verfasserin |4 aut | |
| 700 | 1 | |a Leroux-Roels, Geert |e verfasserin |4 aut | |
| 700 | 1 | |a Bosch, Jacobus J |e verfasserin |4 aut | |
| 700 | 1 | |a Fendel, Rolf |e verfasserin |4 aut | |
| 700 | 1 | |a Kreidenweiss, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Velavan, Thirumalaisamy P |e verfasserin |4 aut | |
| 700 | 1 | |a Fotin-Mleczek, Mariola |e verfasserin |4 aut | |
| 700 | 1 | |a Mueller, Stefan O |e verfasserin |4 aut | |
| 700 | 1 | |a Quintini, Gianluca |e verfasserin |4 aut | |
| 700 | 1 | |a Schönborn-Kellenberger, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Vahrenhorst, Dominik |e verfasserin |4 aut | |
| 700 | 1 | |a Verstraeten, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Alves de Mesquita, Margarida |e verfasserin |4 aut | |
| 700 | 1 | |a Walz, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Wolz, Olaf-Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Oostvogels, Lidia |e verfasserin |4 aut | |
| 700 | 0 | |a CV-NCOV-001 Study Group |e verfasserin |4 aut | |
| 700 | 1 | |a De Boever, Fien |e investigator |4 oth | |
| 700 | 1 | |a Desimpel, Anniek |e investigator |4 oth | |
| 700 | 1 | |a Esen, Meral |e investigator |4 oth | |
| 700 | 1 | |a Fischer, Ina |e investigator |4 oth | |
| 700 | 1 | |a Flügge, Judith |e investigator |4 oth | |
| 700 | 1 | |a Geisenberger, Otto |e investigator |4 oth | |
| 700 | 1 | |a Geldmacher, Christof |e investigator |4 oth | |
| 700 | 1 | |a Held, Katrin |e investigator |4 oth | |
| 700 | 1 | |a Hoffmann, Larissa |e investigator |4 oth | |
| 700 | 1 | |a Hölscher, Michael |e investigator |4 oth | |
| 700 | 1 | |a Huber, Kristina |e investigator |4 oth | |
| 700 | 1 | |a Jacobs, Bart |e investigator |4 oth | |
| 700 | 1 | |a Joye, Jasper |e investigator |4 oth | |
| 700 | 1 | |a Kirschke, Jacqueline |e investigator |4 oth | |
| 700 | 1 | |a Klopp, Norman |e investigator |4 oth | |
| 700 | 1 | |a Koehne, Erik |e investigator |4 oth | |
| 700 | 1 | |a Köhler, Carsten |e investigator |4 oth | |
| 700 | 1 | |a Lalremruata, Albert |e investigator |4 oth | |
| 700 | 1 | |a Lamsfus-Calle, Carlos |e investigator |4 oth | |
| 700 | 1 | |a Linh, Le Thi Kieu |e investigator |4 oth | |
| 700 | 1 | |a Maes, Cathy |e investigator |4 oth | |
| 700 | 1 | |a Metaxa, Dafni |e investigator |4 oth | |
| 700 | 1 | |a Molnar, Marie-Luise |e investigator |4 oth | |
| 700 | 1 | |a Mueller, Mariana |e investigator |4 oth | |
| 700 | 1 | |a Müller-Schöner, Gesine |e investigator |4 oth | |
| 700 | 1 | |a Quindel, Marion |e investigator |4 oth | |
| 700 | 1 | |a Rappe, Sabine |e investigator |4 oth | |
| 700 | 1 | |a Schultze-Naumburg, Liz |e investigator |4 oth | |
| 700 | 1 | |a Schumacher, Carsten |e investigator |4 oth | |
| 700 | 1 | |a Schuster, Sabine |e investigator |4 oth | |
| 700 | 1 | |a Thiel, Verena |e investigator |4 oth | |
| 700 | 1 | |a Vejda, Susanne |e investigator |4 oth | |
| 700 | 1 | |a Waerlop, Gwenn |e investigator |4 oth | |
| 700 | 1 | |a Westenberg, Carola |e investigator |4 oth | |
| 700 | 1 | |a Wons, Katrin |e investigator |4 oth | |
| 700 | 1 | |a Zeder, Andreas |e investigator |4 oth | |
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