title: Safety and immunogenicity of a prototype adjuvanted inactivated split-virus influenza A (H5N1) vaccine in infants and children.
abstract: OBJECTIVE
  Highly pathogenic avian influenza A virus (H5N1) is a leading candidate for the next influenza pandemic, and infants and children may play an important role in transmission in a pandemic. Our objective was to evaluate the safety and immunogenicity of a prototype inactivated, aluminium adjuvanted, split-virus, clade 1 H5N1 vaccine (A/Vietnam/1194/2004/NIBRG-14) in infants and children aged > or =6 months to < 9 years.
  
  
  METHODS
  Healthy infants and children (N=150) received two doses of 30 microg or 45 microg H5 HA with AlPO4 adjuvant 21 days apart. Serum samples were collected for virus microneutralisation (MN) and haemagglutination inhibition (HI) assays on Days 0, 21, and 42. Six-month antibody persistence following second vaccine dose was assessed by MN, and cross-reactive HI antibodies to a clade 2 variant strain (INDO5/RG2) were evaluated at Day 42.
  
  
  RESULTS
  Both formulations were well-tolerated. Two doses of 30 microg or 45 microg H5 HA formulations elicited strong immune responses by both MN (98-99% > or =1:20) and HI assays (95-100% > or =1:32), with 80-87% of children having MN antibody persistence (> or =1:20) up to 6 months post-vaccination. Additionally, robust cross-clade HI antibody responses were elicited following two doses.
  
  
  CONCLUSIONS
  Two doses of prototype 30 microg or 45 microg aluminium-adjuvanted, H5N1 vaccines were highly immunogenic and well-tolerated, with considerable antibody persistence 6 months after the primary vaccination course. Additional cross-clade HI antibody responses and an acceptable safety and tolerability profile support the use of the either candidate vaccine formulations in infants and children in the event of a pandemic.
authors.affiliation: Melbourne School of Population Health, The University of Melbourne, Victoria, Australia. t.nolan@unimelb.edu.au
authors.forename: Terry
authors.initials: T
authors.lastname: Nolan
authors.forename: Peter C
authors.initials: PC
authors.lastname: Richmond
authors.forename: Neil T
authors.initials: NT
authors.lastname: Formica
authors.forename: Katja
authors.initials: K
authors.lastname: Höschler
authors.forename: Maryanne V
authors.initials: MV
authors.lastname: Skeljo
authors.forename: Tanya
authors.initials: T
authors.lastname: Stoney
authors.forename: Jodie
authors.initials: J
authors.lastname: McVernon
authors.forename: Gunter
authors.initials: G
authors.lastname: Hartel
authors.forename: Daphne C
authors.initials: DC
authors.lastname: Sawlwin
authors.forename: Jillian
authors.initials: J
authors.lastname: Bennet
authors.forename: David
authors.initials: D
authors.lastname: Ryan
authors.forename: Russell L
authors.initials: RL
authors.lastname: Basser
authors.forename: Maria C
authors.initials: MC
authors.lastname: Zambon
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000535:Aluminum / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D053124:Influenza A Virus, H5N1 Subtype / Q000145:classification / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D009500:Neutralization Tests; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D000535:Aluminum