tetano
Editor, Senior Moderator
Sci Transl Med
. 2023 Sep 13;15(713):eadf4100.
doi: 10.1126/scitranslmed.adf4100. Epub 2023 Sep 13. Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2
Guillaume B E Stewart-Jones[SUP] 1 [/SUP], Sayda M Elbashir[SUP] 1 [/SUP], Kai Wu[SUP] 1 [/SUP], Diana Lee[SUP] 1 [/SUP], Isabella Renzi[SUP] 1 [/SUP], Baoling Ying[SUP] 2 [/SUP], Matthew Koch[SUP] 1 [/SUP], Caralyn E Sein[SUP] 1 [/SUP], Angela Choi[SUP] 1 [/SUP], Bradley Whitener[SUP] 2 [/SUP], Dario Garcia-Dominguez[SUP] 1 [/SUP], Carole Henry[SUP] 1 [/SUP], Angela Woods[SUP] 1 [/SUP], LingZhi Ma[SUP] 1 [/SUP], Daniela Montes Berrueta[SUP] 1 [/SUP], Laura E Avena[SUP] 1 [/SUP], Julian Quinones[SUP] 1 [/SUP], Samantha Falcone[SUP] 1 [/SUP], Chiaowen J Hsiao[SUP] 1 [/SUP], Suzanne M Scheaffer[SUP] 2 [/SUP], Larissa B Thackray[SUP] 2 [/SUP], Phil White[SUP] 1 [/SUP], Michael S Diamond[SUP] 2 3 4 [/SUP], Darin K Edwards[SUP] 1 [/SUP], Andrea Carfi[SUP] 1 [/SUP]
Affiliations
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).
. 2023 Sep 13;15(713):eadf4100.
doi: 10.1126/scitranslmed.adf4100. Epub 2023 Sep 13. Domain-based mRNA vaccines encoding spike protein N-terminal and receptor binding domains confer protection against SARS-CoV-2
Guillaume B E Stewart-Jones[SUP] 1 [/SUP], Sayda M Elbashir[SUP] 1 [/SUP], Kai Wu[SUP] 1 [/SUP], Diana Lee[SUP] 1 [/SUP], Isabella Renzi[SUP] 1 [/SUP], Baoling Ying[SUP] 2 [/SUP], Matthew Koch[SUP] 1 [/SUP], Caralyn E Sein[SUP] 1 [/SUP], Angela Choi[SUP] 1 [/SUP], Bradley Whitener[SUP] 2 [/SUP], Dario Garcia-Dominguez[SUP] 1 [/SUP], Carole Henry[SUP] 1 [/SUP], Angela Woods[SUP] 1 [/SUP], LingZhi Ma[SUP] 1 [/SUP], Daniela Montes Berrueta[SUP] 1 [/SUP], Laura E Avena[SUP] 1 [/SUP], Julian Quinones[SUP] 1 [/SUP], Samantha Falcone[SUP] 1 [/SUP], Chiaowen J Hsiao[SUP] 1 [/SUP], Suzanne M Scheaffer[SUP] 2 [/SUP], Larissa B Thackray[SUP] 2 [/SUP], Phil White[SUP] 1 [/SUP], Michael S Diamond[SUP] 2 3 4 [/SUP], Darin K Edwards[SUP] 1 [/SUP], Andrea Carfi[SUP] 1 [/SUP]
Affiliations
- PMID: 37703353
- DOI: 10.1126/scitranslmed.adf4100
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).