title: Immunogenicity and safety of AS03-adjuvanted 2009 influenza A H1N1 vaccine in children 6-35 months.
abstract: We report on the evaluation of the immunogenicity and reactogenicity/safety of AS03-adjuvanted vaccine against pandemic influenza A/H1N1/2009 in young children. In this open-label, randomized study, 157 healthy children aged 6-35 months received two doses (21 days apart) of split-virion inactivated A/California/7/2009 H1N1 vaccine containing either (i) 1.9microg hemagglutinin (HA) and AS03(B) (5.93mg tocopherol) (N=104) or (ii) 3.75mug HA and AS03(A) (11.86mg tocopherol) (N=53). At 21 days following the first dose of AS03(B)-adjuvanted vaccine (1.9microg HA) the percentage of children with hemagglutination-inhibition titers of >or=40 against the vaccine strain rose from 3.0% before vaccination to 100%. The seroconversion rate was 99% and the geometric mean titer (GMT) increased from 6 to 313. After the second dose the GMT increased further to 2008. The higher dose AS03(A)-adjuvanted 3.75microg HA vaccine did not further increase the immune response. Solicited symptoms reported within 7 days following vaccination were mainly mild to moderate. After the first dose of AS03(B)-adjuvanted vaccine (1.9microg HA) the most common solicited symptoms were pain at the injection site (35.6%) and irritability (31.7%). Fever (axillary >or=37.5 degrees C) was reported with an incidence of 20.2%. After the second dose reactogenicity tended to increase (injection site pain: 41.3%; irritability: 46.2%; fever >or=37.5 degrees C: 67.3%). Spontaneously reported adverse events with an intensity that prevented normal activities were documented for 2.9-6.7% of doses with only one event (vomiting) considered related to vaccination. There was one serious adverse event reported in the AS03(A)-adjuvanted 3.75microg HA vaccine group (traumatic brain injury) which was not considered as related to vaccination. In conclusion, these data suggest that a first dose of AS03(B)-adjuvanted A/H1N1/2009 vaccine containing 1.9microg HA in children 6-35 months old is highly immunogenic and that the overall reactogenicity profile is acceptable although reactions including fever tend to increase after a second dose.
authors.affiliation: Insituto Hispalense de Pediatría, Sevilla, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carmona
authors.forename: Félix
authors.initials: F
authors.lastname: Omeñaca
authors.forename: Juan C
authors.initials: JC
authors.lastname: Tejedor
authors.forename: Jose M
authors.initials: JM
authors.lastname: Merino
authors.forename: Tejaswini
authors.initials: T
authors.lastname: Vaman
authors.forename: Ilse
authors.initials: I
authors.lastname: Dieussaert
authors.forename: Paul
authors.initials: P
authors.lastname: Gillard
authors.forename: Javier
authors.initials: J
authors.lastname: Arístegui
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D002675:Child, Preschool; D004338:Drug Combinations; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary; 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*; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage; D024502:alpha-Tocopherol / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol