We propose to develop novel, new generation vaccines for viral respiratory disease using multiprotein virus-like particles as the delivery system. The project will concern: (1) the influenza virus A and B and (2) selected paramyxoviruses (parainfluenza and respiratory syncytial virus). We have previously developed a system that allows the synthesis of a multicomponent structure involving capsid core-like particles (CLPs), consisting of VP3 and VP7, and double capsid virus-like particles (VLPs), consisting of VP2, VP3, VP5 and VP7. The CLPs (69 nm in diameter) and VLPs (80nm in diameter) lack nucleic acids and are highly immunogenic in vertebrates (mice, rabbits, sheep. The high level production of CLPs and VLPs from baculovirus vectors and their strong protection capabilities at low doses (10 ug as demonstrated in vertebrate hosts) have enabled us to recently develop them as a carrier system in which foreign antigens can be presented in polyvalent forms to the immune system to induce both cellular and humoral immunity. We propose to construct chimeric genes which will produce VLPs containing immunogenic regions of influenza A and B viruses. The derived chimeric particles will be tested for their protective efficacious using appropriate challenges in post-vaccinated animals. The long therm goal is to make vaccine chimeras containing multiple immunogens representing selected viral pathogens.
| Monastyrskaya, K; Gould, E A; Roy, P (1995) Characterization and modification of the carboxy-terminal sequences of bluetongue virus type 10 NS1 protein in relation to tubule formation and location of an antigenic epitope in the vicinity of the carboxy terminus of the protein. J Virol 69:2831-41 |
