Genetic stability of live, cold-adapted influenza virus components of the FluMist/CAIV-T vaccine throughout the manufacturing process.
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.
Buonagurio
Deborah A
DA
Department of Vaccines Discovery Research, Wyeth Research, 401N. Middletown Road, Pearl River, NY 10965, USA. buonagd@wyeth.com
Bechert
Thomas M
TM
Yang
Chin-Fen
CF
Shutyak
Leonid
L
D'Arco
Gail A
GA
Kazachkov
Yuriy
Y
Wang
Hai-Ping
HP
Rojas
Eduardo A
EA
O'Neill
Robert E
RE
Spaete
Richard R
RR
Coelingh
Kathleen L
KL
Zamb
Timothy J
TJ
Sidhu
Mohinder S
MS
Udem
Stephen A
SA
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
D000336:Aerosols; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated