Respiratory Syncytial Virus (RSV) Vaccines Based on Promoter-Proximate Attenuation

Available for licensing and commercial development is a patent estate and related biological materials for producing therapeutic or prophylactic vaccines against Respiratory Syncytial Virus (RSV). The claimed vaccine strategy relates to the engineering and creation of live-attenuated RSV vaccine candidates by shifting the position of one or more viral genes relative to the viral promoter (aka promoter-proximal attenuation). The gene shifts can be constructed by insertion, deletion or rearrangement of genes or genome segments within the recombinant genome or antigenome. Viral replication can increase or decrease depending on the position of expressed viral gene and depending on the nature and degree of the positional shift. Viral gene rearrangements are selected to maintain sufficient non-infectious replication of RSV while eliciting host anti-RSV immune responses. Viral genes targeted for such rearrangement include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or genome segment.

One modification of particular interest is the placement of the G and F protective antigen genes in a promoter-proximal position for increased expression. The gene position-shifted RSV can be further manipulated by the addition of specific nucleotide and amino acid point mutations or host range restriction determinants to yield desired phenotypic and structural effects.