title: Genetic stability of live, cold-adapted influenza virus components of the FluMist/CAIV-T vaccine throughout the manufacturing process.
abstract: FluMist is a live-attenuated, trivalent influenza vaccine (LAIV) recently approved for intranasal administration. To demonstrate genetic stability during manufacture of the vaccine viruses in LAIV and a similar vaccine in development (CAIV-T), full genome consensus sequences were determined at multiple manufacturing stages for four influenza type A and five type B strains. The critical cold-adapted (ca), temperature-sensitive (ts) and attenuated (att) mutations were preserved in the virus manufacturing intermediates. Moreover, sequence identity was observed for all vaccine intermediates of the same strain. Minor sequence differences were noted in the shared gene segments of the vaccine viruses and their common progenitor master donor virus (MDV) and several of the hemagglutinin (HA) and neuraminidase (NA) genes contained nucleotide differences when compared to the wild-type parent. Nonetheless, all vaccine viruses retained the ca, ts, and att phenotypes. Thus, genetic and phenotypic stability of the vaccine viruses is maintained during the manufacture of LAIV/CAIV-T vaccines.
authors.affiliation: Department of Vaccines Discovery Research, Wyeth Research, 401N. Middletown Road, Pearl River, NY 10965, USA. buonagd@wyeth.com
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Buonagurio
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bechert
authors.forename: Chin-Fen
authors.initials: CF
authors.lastname: Yang
authors.forename: Leonid
authors.initials: L
authors.lastname: Shutyak
authors.forename: Gail A
authors.initials: GA
authors.lastname: D'Arco
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Kazachkov
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Wang
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Rojas
authors.forename: Robert E
authors.initials: RE
authors.lastname: O'Neill
authors.forename: Richard R
authors.initials: RR
authors.lastname: Spaete
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Coelingh
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 / Q000502:physiology*; D000281:Administration, Intranasal; D000336:Aerosols; D003080:Cold Temperature; D009980:Influenza A virus / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D007252:Influenza Vaccines / Q000737:chemistry / Q000235:genetics*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics; D014776:Virus Cultivation
chemical_list: D000336:Aerosols; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated