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.
Hall
S L
SL
Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Sarris
C M
CM
Tierney
E L
EL
London
W T
WT
Murphy
B R
BR
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