Current RSV vaccine candidates have focused on attenuated viruses that incorporate mutations specifying temperature sensitivity. While some of these vaccine candidates were found to be sufficiently attenuated in in-fants, they are only poorly immunogenic. In addition, these mutations are inherently unstable and revert, resulting in partial reversion of the tem-perature sensitivity phenotype. Thus, enhancing the immunogenicity of RSV vaccine candidates, while increasing their genotypic and phenotypic stability is important for the development of a successful RSV vaccine. An additional issue is the ability to produce clinical lots of attenuated vaccine virus due to reduced replication of the vaccine candidates in cell culture. Our invention provides a method for producing live-attenuated RSV vac-cine candidates with enhanced immunogenicity without compromising the ability of the virus to replicate to high titers in suitable cell substrates for vaccine production. This new method has to potential to provide the first license vaccine for RSV since its discovery and provide a much needed preventative treatment for pediatric bronchiolitis.
RSV Vaccines with Improved Immunogenicity