A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28000669.
- Also identified by DOI 10.1038/ncomms13916 and PMC identifier 5187593.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization and there remains no pediatric vaccine. RSV live-attenuated vaccines (LAVs) have a history of safe testing in infants; however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we seek to engineer an RSV LAV with enhanced immunogenicity. Genetic mapping identifies strain line 19 fusion (F) protein residues that correlate with pre-fusion antigen maintenance by ELISA and thermal stability of infectivity in live RSV. We generate a LAV candidate named OE4 which expresses line 19F and is attenuated by codon-deoptimization of non-structural (NS1 and NS2) genes, deletion of the small hydrophobic (SH) gene, codon-deoptimization of the attachment (G) gene and ablation of the secreted form of G. OE4 (RSV-A2-dNS1-dNS2-ΔSH-dG<sub>m</sub>-Gs<sub>null</sub>-line19F) exhibits elevated pre-fusion antigen levels, thermal stability, immunogenicity, and efficacy despite heavy attenuation in the upper and lower airways of cotton rats.
Medical subject headings
- Respiratory Syncytial Virus Infections
- Respiratory Syncytial Virus Vaccines
- Respiratory Syncytial Virus, Human
- Vaccines, Attenuated