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.
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.
| Haller, A A; MacPhail, M; Mitiku, M et al. (2001) A single amino acid substitution in the viral polymerase creates a temperature-sensitive and attenuated recombinant bovine parainfluenza virus type 3. Virology 288:342-50 |
| Haller, A A; Miller, T; Mitiku, M et al. (2000) Expression of the surface glycoproteins of human parainfluenza virus type 3 by bovine parainfluenza virus type 3, a novel attenuated virus vaccine vector. J Virol 74:11626-35 |
