A Cold-Adapted Mutant of Parainfluenza Virus Type 3 Is Attenuated and Protective in Chimpanzees

A live attenuated cold-adapted parainfluenza virus type 3 (PIV-3) vaccine is being developed to prevent the serious lower respiratory tract disease caused by this virus in infants and young children. This cold-passaged mutant (cp45) was evaluated in seronegative chimpanzees and found to be highly attenuated in both the upper and lower respiratory tracts compared to its wild-type parent. Animals immunized with cp45 were also highly resistant to wild-type PIV-3 challenge. Stability of the attenuation phenotype was demonstrated by the administration to 2 additional chimpanzees of an isolate of cp45 obtained after 10 days of replication in a chimpanzee. It was attenuated in both the upper and lower respiratory tracts. The cp45 virus present in the respiratory tract secretions of chimpanzees retained the temperature-sensitive (ts) phenotype, but some loss of ts property was observed in the isolates. These results provide a basis on which to proceed to clinical trials in seronegative human infants and children.