Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2
With the success of messenger RNA (mRNA) vaccines against coronavirus disease 2019, strategies can now focus on improving vaccine potency, breadth, and stability. We designed and evaluated domain-based mRNA vaccines encoding the wild-type spike protein receptor binding domain (RBD) or N-terminal domain (NTD) alone or in combination. An NTD-RBD-linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2° to 8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In BALB/c mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) viruses compared with mRNA-1273-immunized mice, especially at lower vaccine dosages. K18-hACE2 mice immunized with mRNA-1283 or mRNA-1273 as a primary series demonstrated similar degrees of protection from challenge with SARS-CoV-2 Delta and Omicron variants at all vaccine dosages. These results support clinical assessment of mRNA-1283, which has now entered clinical trials (NCT05137236).
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Science translational medicine - 15(2023), 713 vom: 13. Sept., Seite eadf4100 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Stewart-Jones, Guillaume B E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.09.2023 Date Revised 12.10.2023 published: Print-Electronic ClinicalTrials.gov: NCT05137236 UpdateOf: bioRxiv. 2022 Oct 07;:. - PMID 36238717 Citation Status MEDLINE |
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| doi: |
10.1126/scitranslmed.adf4100 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362006725 |
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| 245 | 1 | 0 | |a Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2 |
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| 500 | |a ClinicalTrials.gov: NCT05137236 | ||
| 500 | |a UpdateOf: bioRxiv. 2022 Oct 07;:. - PMID 36238717 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a With the success of messenger RNA (mRNA) vaccines against coronavirus disease 2019, strategies can now focus on improving vaccine potency, breadth, and stability. We designed and evaluated domain-based mRNA vaccines encoding the wild-type spike protein receptor binding domain (RBD) or N-terminal domain (NTD) alone or in combination. An NTD-RBD-linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2° to 8°C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In BALB/c mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) viruses compared with mRNA-1273-immunized mice, especially at lower vaccine dosages. K18-hACE2 mice immunized with mRNA-1283 or mRNA-1273 as a primary series demonstrated similar degrees of protection from challenge with SARS-CoV-2 Delta and Omicron variants at all vaccine dosages. These results support clinical assessment of mRNA-1283, which has now entered clinical trials (NCT05137236) | ||
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| 700 | 1 | |a Elbashir, Sayda M |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Diana |e verfasserin |4 aut | |
| 700 | 1 | |a Renzi, Isabella |e verfasserin |4 aut | |
| 700 | 1 | |a Ying, Baoling |e verfasserin |4 aut | |
| 700 | 1 | |a Koch, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Sein, Caralyn E |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Whitener, Bradley |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia-Dominguez, Dario |e verfasserin |4 aut | |
| 700 | 1 | |a Henry, Carole |e verfasserin |4 aut | |
| 700 | 1 | |a Woods, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, LingZhi |e verfasserin |4 aut | |
| 700 | 1 | |a Montes Berrueta, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Avena, Laura E |e verfasserin |4 aut | |
| 700 | 1 | |a Quinones, Julian |e verfasserin |4 aut | |
| 700 | 1 | |a Falcone, Samantha |e verfasserin |4 aut | |
| 700 | 1 | |a Hsiao, Chiaowen J |e verfasserin |4 aut | |
| 700 | 1 | |a Scheaffer, Suzanne M |e verfasserin |4 aut | |
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| 700 | 1 | |a Edwards, Darin K |e verfasserin |4 aut | |
| 700 | 1 | |a Carfi, Andrea |e verfasserin |4 aut | |
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