Design and preclinical assessment of mRNA-1345 prefusion F glycoprotein-encoding mRNA vaccine for respiratory syncytial virus
Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract disease in young children and older adults. We designed a codon-optimized mRNA vaccine, mRNA-1345, encoding the RSV F-glycoprotein stabilized in the prefusion (preF) conformation and with a deletion at the cytoplasmic tail. mRNA-1345 cell surface protein expression was higher and detected for longer versus previous mRNA-based RSV vaccine candidates evaluated clinically. In rodent models, mRNA-1345 induced a robust neutralizing and preF-biased antibody response, a T helper 1-biased cellular response, and demonstrated dose-dependent protection against RSV challenge with no evidence of enhanced respiratory disease. These results supported initial clinical evaluation of mRNA-1345 in adults, children, and RSV-naïve infants; mRNA-1345 was recently demonstrated to be efficacious against RSV disease in older adults in a pivotal efficacy study.
Authors
- Edison Ong (ORCID: https://orcid.org/0000-0002-5159-414X)
- Andrea Carfı́ (ORCID: https://orcid.org/0000-0001-5508-3809)
- Christine A. Shaw (ORCID: https://orcid.org/0000-0002-0471-206X)
- Sachin Mani (ORCID: https://orcid.org/0000-0003-2974-6853)
- Guillaume B. E. Stewart-Jones (ORCID: https://orcid.org/0000-0002-2440-3790)
- Patricia A. Jorquera (ORCID: https://orcid.org/0000-0002-8111-5138)
- Tatiana Ketova
- Sayda M. Elbashir (ORCID: https://orcid.org/0000-0001-6250-9679)
- LingZhi Ma (ORCID: https://orcid.org/0000-0001-6405-7100)
- Angela Woods (ORCID: https://orcid.org/0009-0008-0225-6815)
- Amy E. Rabideau (ORCID: https://orcid.org/0000-0002-3433-6050)
- Vladimir Presnyak (ORCID: https://orcid.org/0000-0001-6695-7102)
- Elisabeth Narayanan (ORCID: https://orcid.org/0000-0001-8836-181X)
- Cosmin Teodor Mihai (ORCID: https://orcid.org/0000-0002-0945-5437)
- Paulina Kapłonek (ORCID: https://orcid.org/0000-0001-9459-5946)
- Erin Hanahoe
- David W. Reid (ORCID: https://orcid.org/0000-0001-9517-8212)
- Nicole Hunter
Institutions
- Moderna Therapeutics (United States) (US)
Publication Details
- Journal
- Vaccine
- Published
- 2025-08-20
- DOI
- https://doi.org/10.1016/j.vaccine.2025.127589
- Citations
- 5
- Primary Topic
- Respiratory viral infections research
- Type
- article
- Field-Weighted Citation Impact
- 6.77
Funders
- Moderna