title: Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children.
abstract: Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months-17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 μg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 μg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1-<3, 3-8, and 9-17 y cohorts; however, 2 vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1-<3 and 3-8 y cohorts. Among children aged 6-11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children <12 months) and 7.5_fullMF59 vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people.
authors.affiliation: a Clinic for Children and Youth; Dr. Horst Schmidt Clinics ; Wiesbaden , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Knuf
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.forename: Hans
authors.initials: H
authors.lastname: Rümke
authors.forename: Luis
authors.initials: L
authors.lastname: Rivera
authors.forename: Paola
authors.initials: P
authors.lastname: Pedotti
authors.forename: Ashwani Kumar
authors.initials: AK
authors.lastname: Arora
authors.forename: Maria
authors.initials: M
authors.lastname: Lattanzi
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kieninger
authors.forename: Giovanni Della
authors.initials: GD
authors.lastname: Cioppa
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D064368:Healthy Volunteers; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D009500:Neutralization Tests; D011136:Polysorbates / Q000008:administration & dosage* / Q000009:adverse effects; D016037:Single-Blind Method; D013185:Squalene / Q000008:administration & dosage* / Q000009:adverse effects; D014611:Vaccination / Q000009:adverse effects* / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene
keywords: AE, adverse event; CHMP, European Committee for Medicinal Products for Human Use; CI, confidence interval; GMR, geometric mean ratio; GMT, geometric mean titer; H1N1; HI, hemagglutination inhibition; MF59; MN, microneutralization; PPS, per-protocol set; SAE, serious adverse event; WHO, World Health Organization; adjuvant; cell-culture; pandemic; pediatric