title: Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.
abstract: In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.
authors.affiliation: a University Children Hospital La Paz ; Madrid , Spain.
authors.forename: José
authors.initials: J
authors.lastname: Garcia-Sicilia
authors.affiliation: b Hospital Universitario Basurto ; Bilbao , Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Arístegui
authors.affiliation: a University Children Hospital La Paz ; Madrid , Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Omeñaca
authors.affiliation: c Insituto Hispalense de Pediatría ; Seville , Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carmona
authors.affiliation: d Mostoles Hospital ; Madrid , Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Tejedor
authors.affiliation: e Hospital General Yagüe ; Burgos , Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Merino
authors.affiliation: f GSK ; Madrid , Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Corbeira
authors.affiliation: g GSK Vaccines ; Rixensart , Belgium.
authors.forename: Karl
authors.initials: K
authors.lastname: Walravens
authors.affiliation: h Quanticate ; Bangalore , India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Bambure
authors.affiliation: g GSK Vaccines ; Rixensart , Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.affiliation: g GSK Vaccines ; Rixensart , Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Caplanusi
authors.affiliation: i GSK Vaccines ; Wavre , Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Gillard
authors.affiliation: g GSK Vaccines ; Rixensart , Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Dieussaert
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage* / Q000009:adverse effects; D013185:Squalene / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol
keywords: AS03 adjuvant; H1N1 pandemic vaccine; cell-mediated immunity; children; haemagglutinin inhibition; microneutralisation; persistence; safety