title: Safety and immunogenicity of an MF59-adjuvanted A/H1N1 pandemic influenza vaccine in children from three to seventeen years of age.
abstract: OBJECTIVE
  This study was designed to identify the optimal dose of an MF59-adjuvanted, monovalent, A/H1N1 influenza vaccine in healthy paediatric subjects.
  
  
  METHODS
  Subjects aged 3-8 years (n=194) and 9-17 years (n=160) were randomized to receive two primary doses of A/H1N1 vaccine containing either 3.75 μg antigen with half a standard dose of MF59 adjuvant, 7.5 μg antigen with a full dose of MF59, or (children 3-8 years only), a non-adjuvanted 15 μg formulation. A booster dose of MF59-adjuvanted seasonal influenza vaccine including homologous A/H1N1 strain was given one year after priming. Immunogenicity was assessed by haemagglutination inhibition (HI) and microneutralization assays. Vaccine safety was assessed throughout the study (up to 18 months).
  
  
  RESULTS
  A single priming dose of either MF59-adjuvanted formulation was sufficient to meet the European licensure criteria for pandemic influenza vaccines (HI titres ≥1:40>70%; seroconversion>40%; and GMR>2.5). Two non-adjuvanted vaccine doses were required to meet the same licensure criteria. After first and second doses, percentage of subjects with HI titres ≥1:40 were between 97% and 100% in the adjuvanted vaccine groups compared with 68% and 91% in the non-adjuvanted group, respectively. Postvaccination seroconversion rates ranged from 91% to 98% in adjuvanted groups and were 68% (first dose) and 98% (second dose) in the non-adjuvanted group. HI titres ≥1:330 after primary doses were achieved in 69% to 90% in adjuvanted groups compared with 41% in the non-adjuvanted group. Long-term antibody persistence after priming and a robust antibody response to booster immunization were observed in all vaccination groups. All A/H1N1 vaccine formulations were generally well tolerated. No vaccine-related serious adverse events occurred, and no subjects were withdrawn from the study due to an adverse event.
  
  
  CONCLUSIONS
  An MF59-adjuvanted influenza vaccine containing 3.75 μg of A/H1N1 antigen was well tolerated and sufficiently immunogenic to meet all the European licensure criteria after a single dose in healthy children 3-17 years old.
authors.affiliation: Zentrum für Kinder-und Jugendmedizin, Universitätsmedizin, Mainz, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Knuf
authors.affiliation: Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.affiliation: Vaxinostics BV, University Vaccine Center Rotterdam Nijmegen, Rotterdam, The Netherlands.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Rümke
authors.affiliation: Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile.
authors.forename: Katia
authors.initials: K
authors.lastname: Abarca
authors.affiliation: Hospital Maternidad Ntra Sra. de la Altagracia, Gazcue, Santo Domingo, The Dominican Republic.
authors.forename: Luis
authors.initials: L
authors.lastname: Rivera
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l., Siena, Italy. Electronic address: maria.lattanzi@novartis.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Lattanzi
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l., Siena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Pedotti
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l., Siena, Italy.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Arora
authors.affiliation: Zentrum für Kinder-und Jugendmedizin, Universitätsmedizin, Mainz, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kieninger-Baum
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l., Siena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Della Cioppa
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; D005260:Female; 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*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D009500:Neutralization Tests; D011136:Polysorbates / Q000008:administration & dosage / Q000009:adverse effects*; D013185:Squalene / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene
keywords: A/H1N1; MF59; Paediatric; Pandemic influenza; Vaccine; www.clinicaltrials.gov (NCT00971542)