Related Experiment Video
Updated: May 24, 2026
11:48
Generation, Amplification, and Titration of Recombinant Respiratory Syncytial Viruses
Published on: April 4, 2019
Dynamic regulation-based stabilizing mutations are highly effective for designing RSV pre-fusion F mRNA vaccines
Shuai Shao1, Ze Yuan Dong2, Zi Yao Kang3
1The Sixth Laboratory, National Vaccine and Serum Institute (NVSI), Beijing, 101111, China; National Engineering Center for New Vaccine Research, Beijing, 101111, China.
Biochemical and Biophysical Research Communications
|May 22, 2026
Summary
A novel messenger RNA (mRNA) vaccine candidate targeting respiratory syncytial virus (RSV) demonstrated superior immunogenicity and protection in mice. This RSV mRNA vaccine, based on a stabilized F protein, shows promise for future vaccine development.
Area of Science:
- Vaccinology
- Virology
- Molecular Biology
Background:
- Respiratory syncytial virus (RSV) causes severe respiratory infections, particularly in vulnerable populations.
- Existing protein-based RSV vaccines may have limitations for mRNA vaccine development.
- Stabilized pre-fusion F protein (pre-F) strategies are crucial for effective RSV vaccine design.
Purpose of the Study:
- To develop and evaluate an mRNA vaccine candidate based on the pre-fusion stabilized F protein, TriM-5.
- To assess the efficacy of dynamic regulation-based stabilizing mutations in an mRNA vaccine format.
- To optimize the mRNA coding sequence (CDS) for enhanced immunogenicity.
Main Methods:
- Designed a TriM-5 mRNA vaccine candidate with codon optimization using NVSI_GAmRNAopt software.
- Encapsulated the mRNA using lipid nanoparticles (LNPs).
- Performed mouse immunization studies, including antibody titer measurements, cytokine analysis, and virus challenge experiments.
Main Results:
- Codon optimization of the mRNA CDS increased IgG antibody titers approximately threefold.
- The TriM-5 mRNA-LNP induced 3.03-fold higher neutralizing antibody titers compared to a Moderna RSV mRNA sequence.
- Both TriM-5 mRNA-LNP and Moderna mRNA-LNP effectively reduced lung viral loads with no significant lung pathology.
Conclusions:
- The TriM-5 mRNA-LNP vaccine candidate demonstrates superior immunogenicity and protective efficacy against RSV in a mouse model.
- The codon optimization algorithm and stabilizing mutations are effective in the mRNA vaccine format.
- This TriM-5 mRNA-LNP holds significant potential for future RSV vaccine development.
Related Concept Videos
01:29Translational Regulation
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
01:53RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
02:28Leaky Scanning
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
01:23Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
00:36Viral Mutations
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...