Recombinant Sendai Virus as Novel Paramyxovirus Vaccine

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Respiratory syncytial virus (RSV) and human parainfluenza viruses (hPIV) types 1 and 3 are the most common causes of acute viral respiratory disease in infants and young children. Currently, no safe and effective RSV or PIV vaccine has been developed for the prevention of these pathogens. The objective of the multi-project program is to develop a multivalent vaccine using novel Sendal virus recombinants (rSV), generated by reverse genetic techniques, to deliver critical antigens of RSV and hPIV-3 to the pediatric population. In addition, the SV backbone will provide immunity against hPIV-1 based on relatedness of these two type 1 parainfluenza viruses. The Specific Aims of Project 1 descdbe our strategy to meet these objectives: Specific Aim 1: To construct and characterize a set of rSV expressing the envelope glycoproteins of hPIV-3 and RSV (types A and B), yielding a cocktail of first generation recombinants. Specific Aim 2: To compare the growth and target gene expression of rSV expressing membrane-bound versus secreted forms of the target glycoproteins of RSV and hPIV-3. Specific Aim 3: To prepare and characterize purified RSV and hPIV3 envelope glycoproteins, as a source of material for ELISA monitoring of antibody response and for possible boosting of rSV primed responses. This Project is highly related to the other two Projects in this application, rSV constructs, which differ according to the mode of the target antigen expression will be evaluated for immunogenicity by Project 2 investigators. Superior rSV will thus be selected and prepared in a formulation for the evaluation of safety and protection in a non-human primate model in Project 3. The combined Aims of Projects 1, 2 and 3 are intended to advance a SV-based respiratory virus vaccine to human trial for the prevention of serious respiratory virus infections in children.