Competitive Advantages:
Enhanced immunogenicity, Increased genotypic and phenotypic stability, Able to replicate to high titers in suitable cell substrates for vaccine production.
Embodiments disclosed herein provide compositions, methods, and uses for respiratory syncytial viruses (RSV) and immunogenic compositions thereof. Certain embodiments provide RSV having a mutated NSl protein, where the mutation causes the uncoupling of the NSl protein's replication and type I interferon (IFN) antagonist functions. In some embodiments, this uncoupling can produce virions capable of inducing a strong, long-lasting innate immune response while maintaining its ability to replicate in vitro. Also provided are methods for amplifying RSV in host cells, wherein amplified RSV has mutated NS! protein in which the protein's replication and IFN antagonistic functions are uncoupled. In certain embodiments, the amplified RSV having mutated NS! protein is formulated into immunogenic compositions, including vaccines. Other embodiments provide methods for inducing an effective immune response against RSV infection in a subject.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.
