Open AccessPhase II , randomized, open, controlled study of AS 03‐adjuvanted H5N1 pre‐pandemic influenza vaccine in children aged 3 to 9 years: follow‐up of safety and immunogenicity persistence at 24 months post‐vaccination
Author(s) -
DíezDomingo Javier,
Baldó JoséMaría,
PlanellesCatarino Maria Victoria,
GarcésSánchez María,
Ubeda Isabel,
Jubert–Rosich Angels,
Marès Josep,
GarciaCorbeira Pilar,
Moris Philippe,
Teko Maurice,
Vanden Abeele Carline,
Gillard Paul
Publication year - 2015
Publication title -
influenza and other respiratory viruses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.743
H-Index - 57
eISSN - 1750-2659
pISSN - 1750-2640
DOI - 10.1111/irv.12295
Subject(s) - immunogenicity , medicine , vaccination , trivalent influenza vaccine , immunology , influenza a virus subtype h5n1 , population , immune system , adjuvant , influenza vaccine , reactogenicity , live attenuated influenza vaccine , virology , virus , environmental health
Background An AS 03‐adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3–9 years. Methods In this follow‐up of the Phase II study, we report immunogenicity persistence and safety at 24 months post‐vaccination in children aged 3–9 years. The randomized, open‐label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS 03 A or AS03 B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune‐mediated diseases ( pIMD s). Immunogenicity was assessed by hemagglutination‐inhibition assay 12 and 24 months after vaccination; cross‐reactivity and cell‐mediated responses were also assessed. (NCT00502593). Results The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMD s, of which four occurred in H5N1 vaccine recipients, including uveitis ( n = 1) and autoimmune hepatitis ( n = 1), which were considered to be vaccine‐related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell‐mediated immunity was strong, and CD 4 + T cells with a T H 1 profile were observed. Conclusions Two doses of an AS 03‐adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell‐mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination.