title: Live subgroup B respiratory syncytial virus vaccines that are attenuated, genetically stable, and immunogenic in rodents and nonhuman primates.
abstract: Optimal immunization of neonates against disease caused by respiratory syncytial virus (RSV) probably will require multiple doses of a vaccine containing viruses of both subgroups A and B. Live subgroup B RSV mutants were generated containing multiple attenuating mutations, ts (temperature-sensitive) and non-ts (host range), that were introduced by prolonged passage in cell culture or by chemical mutagenesis. The cold-passaged (cp)-52 mutant was restricted in replication compared to wild type virus in rodents and nonhuman primates. In addition, the attenuation phenotype of cp-52 was stable after prolonged replication in immunosuppressed rodents. One or two ts mutations were then introduced into the cp-52 mutant to generate additional candidate vaccine strains that were more attenuated in vivo than the cp-52 parental virus. Tests in humans are being done to determine if one or more of the RSV B-1 mutants exhibit a satisfactory balance between attenuation and immunogenicity.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Crowe
authors.forename: P T
authors.initials: PT
authors.lastname: Bui
authors.forename: C Y
authors.initials: CY
authors.lastname: Firestone
authors.forename: M
authors.initials: M
authors.lastname: Connors
authors.forename: W R
authors.initials: WR
authors.lastname: Elkins
authors.forename: R M
authors.initials: RM
authors.lastname: Chanock
authors.forename: B R
authors.initials: BR
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D016296:Mutagenesis; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D012703:Serotyping; D016205:Sigmodontinae; D014613:Vaccines, Attenuated / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines