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Published on: May 2, 2011
Design and preclinical assessment of mRNA-1345 prefusion F glycoprotein-encoding mRNA vaccine for respiratory
Christine A Shaw1, Guillaume B E Stewart-Jones1, Patricia Jorquera1
1Moderna, Inc., 325 Binney St, Cambridge, MA 02142, USA.
Abstract:
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.
Insights
A new mRNA vaccine, mRNA-1345, shows strong protection against Respiratory Syncytial Virus (RSV) in older adults. This vaccine candidate demonstrated efficacy in clinical trials, offering hope for preventing RSV disease.
Area of Science:
- Vaccinology
- Virology
- Immunology
Background:
- Respiratory Syncytial Virus (RSV) poses a significant health risk, causing severe lower respiratory tract disease in vulnerable populations like young children and older adults.
- Existing vaccine strategies for RSV have limitations, necessitating the development of novel and effective immunization approaches.
Purpose of the Study:
- To evaluate the immunogenicity and efficacy of mRNA-1345, a novel mRNA vaccine candidate targeting the RSV F-glycoprotein.
- To assess the safety profile of mRNA-1345, including the absence of enhanced respiratory disease.
Main Methods:
- Development of a codon-optimized mRNA vaccine (mRNA-1345) encoding a stabilized prefusion RSV F-glycoprotein (preF).
- Assessment of protein expression, antibody responses (neutralizing and preF-biased), and cellular responses (Th1-biased) in preclinical rodent models.
- Evaluation of dose-dependent protection against RSV challenge in animal models.
- Clinical trials in adults, children, and infants, including a pivotal efficacy study in older adults.
Main Results:
- mRNA-1345 exhibited enhanced and prolonged cell surface protein expression compared to prior mRNA RSV vaccine candidates.
- Preclinical studies demonstrated robust neutralizing and preF-biased antibody responses, along with Th1-biased cellular immunity.
- The vaccine showed dose-dependent protection against RSV challenge in rodent models without evidence of enhanced respiratory disease.
- A pivotal efficacy study confirmed mRNA-1345's effectiveness against RSV disease in older adults.
Conclusions:
- mRNA-1345 is a promising mRNA vaccine candidate for preventing RSV disease.
- The vaccine elicits strong immune responses and demonstrates efficacy, particularly in older adults.
- Further clinical evaluation in diverse age groups, including infants, is supported by these findings.
