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A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation.

Nat Commun. 2016; 
Stobart CC,, Rostad CA,, Ke Z, Dillard RS,, Hampton CM,, Strauss JD,, Yi H, Hotard AL,, Meng J,, Pickles RJ, Sakamoto K, Lee S,, Currier MG,, Moin SM, Graham BS, Boukhvalova MS, Gilbert BE, Blanco JC, Piedra PA,, Wright ER,,, Moore ML,.
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Codon Optimization The coding region of codon-deoptimized G (dG) was synthesized by GenScript and cloned by restriction digestion and ligation into the A2-K-dNSh-DSH-line19F(I557V) BAC yielding A2-K-dNSh-DSH-dG- line19F(I557V) yielding the recovery BAC for OE4. Get A Quote

摘要

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 ... More

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