SBIR-STTR Award

Bovine parainfluenza type 3 virus (bPIV3) was shown in clinical trials to be safe when administered to small infants and children, and attenuated, causing no lower respiratory disease in children. bPIV3 was genetically stable after replication in children. These three characteristics provide the basis for the use of bPIV3 as an effective vector vehicle to deliver foreign antigens. Recently, an infectious cDNA of bPIV3 was engineered at Aviron that permits the isolation of recombinant viruses by reverse genetics. This Phase I SBIR proposal will demonstrate the feasibility of this approach by introducing the surface glycoproteins of human parainfluenza virus types l, 2 and 3 (hPIV1, 2, 3) and human respiratory syncytial virus (hRSV) (subgroups A and B) into the genetic genome of bPIV3. Both, hPIV and hRSV. are the causes of upper and lower respiratory disease in infants, children, and immunocompromised or elderly adults, resulting not only in significant numbers of hospitalizations but also in morbidity. No vaccine is currently available for either PIV or RSV associated disease and subunit approaches have so far failed. A Phase II SBIR grant will be used to complete preclinical testing in a subhuman primate model and to initiate human clinical trials. PROPOSED COMMERCIAL APPLICATIONS: The ultimate product of these studies are live attenuated human parainfluenza virus (types l, 2 and 3) and human respiratory syncytial virus (subgroups A and B) vaccines using bovine parainfluenza virus 3 as a vector.

Human parainfluenza virus (hPIV) and human respiratory syncytial virus (hRSV) are the main causes of acute respiratory diseases during infancy and early childhood worldwide, often requiring hospitalization. Both viruses are also responsible for serious respiratory tract infections in elderly and immunocompromised individuals. No vaccines are currently available to prevent PlV or RSV infection and disease. Aviron proposes to develop live, attenuated vaccines for prevention of disease caused by hPIV and hRSV. A novel bovine PIV3 (bPIV3) virus rescue system, using this proven safe vaccine, was established successfully at Aviron using reverse genetics. In the Phase I SBIR grant period, we used bPIV3 as a virus vector to express the hPIV3 and hRSV (subgroup A) surface glycoproteins. In phase II of the SBIR program, clinical trial material of the two vaccine candidates will be used to evaluate their attenuation, immunogenicity, and efficacy in primates. In addition, the bPIV3 vector will be employed to generate hPIV 1, 2 and hRSV subgroup B vaccines using novel molecular approaches. Our goal is to generate bPIV3-vectored vaccines for hPIV1, 2, 3 and hRSV (A and B) for human clinical trials and commercial development. PROPOSED COMMERCIAL APPLICATIONS: Aviron's goal is to produce live, attenuated hPIV and hRSV vaccines using bPIV3 as a virus vaccine vector for prevention of diseases caused by hPIV 1, 2, and 3 and hRSV(subgroups A and B) infection. These vaccines will fill a current unmet health need.