Vaccine with a mutated live-attenuated virus for respiratory syncytial virus (RSV) treatment.
- Is stable and unlikely to revert back to wild-type virus.
- Contains mutations in the genes encoding nonstructural protein, rather than the genes encoding viral coat proteins.
- Expresses 75% less nonstructural protein compared to wild type, but retains 100% expression of wild type nucleoproteins.
RSV is a major cause of lower respiratory track infections in infants, children, and the elderly. Currently, no RSV vaccine exists. RSV vaccine development has faced challenges including high reversion rate and low immunogenicity. There is an urgent need to develop vaccines that provide a long lasting, highly immunogenic response. An effective RSV vaccine has the potential to be administered to all infants as part of routine childhood immunization.
The RSV virion consists of single stranded RNA genetic data, a protein coat, and an envelope that surrounds the protein coat. In addition to the mature viral particle, RSV encodes nonstructural proteins that act within the host cell to suppress an immune response. Most vaccine development has focused on mutating the viral coat, specifically the F and G proteins of the virus. Dr. Moore and colleagues have used an alternative strategy, focused on mutating the genes of the virus that encode nonstructural proteins in order to create a stable, live-attenuated RSV strain. Using a technique called codon de-optimization, a recombinant RSV strain was generated with reduced translational efficiency for the nonstructural genes that results in less expression of the nonstructural proteins. Approximately 20% of the codons of the nonstructural gene are de-optimized, significantly decreasing the likelihood of the mutated virus reverting back to wild type. This technique conserves a limited amount of expression of the nonstructural proteins which promotes higher immunogenicity compared to complete inactivation. Additionally through the codon de-optimization technique, the challenge of viral reversion is largely eliminated. This recombinant RSV strain serves as a promising live, attenuated, vaccine candidate for RSV.
- This RSV strain express 75% less nonstructural proteins and replicates as efficiently as a wild type virus in vitro.
- In vivo testing is ongoing.
View our feature innovation