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.
Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
S L
SL
Hall
C M
CM
Sarris
E L
EL
Tierney
W T
WT
London
B R
BR
Murphy
D000222:Adaptation, Physiological; D000818:Animals; D003080:Cold Temperature; D009154:Mutation; D002679:Pan troglodytes; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D018184:Paramyxoviridae Infections / Q000517:prevention & control*; D010641:Phenotype; D014613:Vaccines, Attenuated / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication
D014613:Vaccines, Attenuated; D014765:Viral Vaccines