title: Human parainfluenza virus type I (HPIV1) vaccine candidates designed by reverse genetics are attenuated and efficacious in African green monkeys.
abstract: A set of recombinant, live attenuated human parainfluenza virus type 1 (rHPIV1) vaccine candidates was evaluated for attenuation, immunogenicity, and protective efficacy in African green monkeys (AGMs). Temperature sensitive (ts) and non-ts attenuating (att) mutations in the P/C and L genes were introduced individually or in various combinations into rHPIV1, including the C(R84G) and HN(T553A) mutations identified in the present work and the C(F170S), L(Y942A), and L(L992C) mutations identified previously. The rHPIV1 vaccine candidates exhibited a spectrum of attenuation in AGMs. One genetically and phenotypically stable vaccine candidate, rC(R84G/F170S)L(Y942A/L992C), was attenuated and efficacious in AGMs and is a promising live attenuated intranasal HPIV1 vaccine candidate suitable for clinical evaluation.
authors.affiliation: Laboratory of Infectious Diseases, Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 50, Room 6511, 50 South Drive MSC 8007, Bethesda, MD 20892-8007, USA. EBartlett@niaid.nih.gov
authors.forename: Emmalene J
authors.initials: EJ
authors.lastname: Bartlett
authors.forename: Emerito
authors.initials: E
authors.lastname: Amaro-Carambot
authors.forename: Sonja R
authors.initials: SR
authors.lastname: Surman
authors.forename: Jason T
authors.initials: JT
authors.lastname: Newman
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Mario H
authors.initials: MH
authors.lastname: Skiadopoulos
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D008253:Macaca mulatta; D022241:Parainfluenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010222:Parainfluenza Virus 1, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D017354:Point Mutation; D010253:Respirovirus Infections / Q000517:prevention & control; D013696:Temperature; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D022241:Parainfluenza Vaccines; D014613:Vaccines, Attenuated; D014764:Viral Proteins