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Attenuation of Human Respiratory Viruses by Synonymous Genome Recoding
Cyril Le Nouën1, Peter L Collins1, Ursula J Buchholz1
1RNA Viruses Section, LID, NIAID, NIH, Bethesda, MD, United States.
Frontiers in Immunology
|June 25, 2019
Summary
Scientists are using synonymous recoding to engineer safer live-attenuated vaccines against viruses like respiratory syncytial virus (RSV) and influenza A virus (IAV). This method modifies viral genomes to reduce pathogen fitness while maintaining essential immune epitopes.
Area of Science:
- Virology
- Synthetic Biology
- Vaccinology
Background:
- Traditional vaccine development faces challenges in achieving optimal safety and efficacy.
- Engineering viral genomes offers a novel approach to vaccine design.
Purpose of the Study:
- To explore synonymous recoding strategies for generating attenuated RNA viruses.
- To assess the potential of these strategies for creating live-attenuated vaccines against human pathogens.
Main Methods:
- Computer algorithms and commercial DNA synthesis were used to recode viral genomes.
- Synonymous recoding strategies included codon deoptimization, increased CpG/UpA content, and introduction of nonsense codon mutations.
- Reverse genetics was employed to generate and characterize engineered viruses.
Main Results:
- Synonymous recoding successfully reduced pathogen fitness and created attenuated viral strains.
- Engineered viruses maintained essential epitopes, suggesting preserved immunogenicity.
- Initial characterization of attenuated respiratory syncytial virus (RSV) and influenza A virus (IAV) showed promising results, alongside some unexpected instability.
Conclusions:
- Genome recoding, synthetic biology, and reverse genetics offer a powerful platform for developing live-attenuated RNA virus vaccines.
- Synonymous recoding presents a strategy to reduce viral de-attenuation and enhance immunogenicity.
- Further research is needed to address the phenotypic and genetic instability observed in some recoded viral candidates.
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