title: Genetic and phenotypic stability of cold-adapted influenza viruses in a trivalent vaccine administered to children in a day care setting.
abstract: The genetic and phenotypic stability of viruses isolated from young children following intranasal administration of the trivalent live-attenuated influenza virus vaccine (LAIV, marketed in the United States as FluMist) was evaluated by determination of genomic sequence and assessment of the cold-adapted (ca), temperature-sensitive (ts) and attenuated (att) phenotypes. The complete genomic sequence was determined for 56 independent isolates obtained from children following vaccination (21 type A/H1N1, 12 A/H3N2, 1 A/H3N1 and 22 type B viruses), 20% of which had no nucleotide misincorporations compared with administered vaccine. The remaining isolates had from one to seven changes per genome. None of the observed misincorporations resulted in predicted amino acid codon substitutions at sites previously shown to contribute to the ca, ts or att phenotypes, and all vaccine-derived isolates retained ca and ts phenotypes consistent with the observation that none of the vaccine recipients displayed distinctive symptoms. The results indicate that LAIV strains undergo very limited genetic change following replication in vaccine recipients and that those changes did not affect vaccine attenuation.
authors.affiliation: Department of Vaccines Discovery Research, Wyeth Research, 401 North Middletown Rd., Pearl River, NY 10965, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Buonagurio
authors.forename: Robert E
authors.initials: RE
authors.lastname: O'Neill
authors.forename: Leonid
authors.initials: L
authors.lastname: Shutyak
authors.forename: Gail A
authors.initials: GA
authors.lastname: D'Arco
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bechert
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Kazachkov
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Wang
authors.forename: Joanne
authors.initials: J
authors.lastname: DeStefano
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Coelingh
authors.forename: Marilyn
authors.initials: M
authors.lastname: August
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Parks
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Zamb
authors.forename: Mohinder S
authors.initials: MS
authors.lastname: Sidhu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Udem
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002656:Child Day Care Centers; D002675:Child, Preschool; D003080:Cold Temperature; D005260:Female; D005289:Ferrets; D006801:Humans; D007114:Immunization; D007223:Infant; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics; D009981:Influenza B virus / Q000235:genetics / Q000254:growth & development; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics* / Q000276:immunology; D008297:Male; D009305:Nasopharynx / Q000382:microbiology
chemical_list: D007252:Influenza Vaccines