title: Predictors of immune response and reactogenicity to AS03B-adjuvanted split virion and non-adjuvanted whole virion H1N1 (2009) pandemic influenza vaccines.
abstract: In 2009, 943 children aged 6 months to 10 years were randomised to receive two doses of an oil-in water AS03B-adjuvanted split virion or a non-adjuvanted whole virion H1N1 (2009) vaccine. The large numbers allowed investigation of possible predictors of immune response and reactogenicity. We used regression analysis to examine the effect of variables including past receipt of seasonal vaccine, antipyretics post-vaccination, interval between doses and pre-existing antibodies to H1N1 (2009) on immunogenicity. We also examined the relationship between immunogenicity and reactogenicity and whether prior infection or underlying conditions affected reactogenicity. For both vaccines, haemagglutination-inhibition titres were 60% higher in children with fever ≥38 °C after vaccination and 29% lower in those previously given seasonal vaccine. Early use of antipyretics did not affect immunogenicity. Post-vaccination titres were higher with longer intervals between doses and in those with evidence of prior infection, but reactogenicity in the latter was unaffected. In the adjuvanted vaccine group, reactions were more common in children with atopy. Both vaccines were safe and immunogenic in those with prior infection. Reduction in the interval between doses for earlier protection would be at the cost of reduced immunogenicity. The effect of seasonal vaccine on immunogenicity merits further investigation.
authors.affiliation: Department of Statistics, Modelling and Economics, Health Protection Services, Health Protection Agency, Colindale, London NW9 5EQ, UK. nick.andrews@hpa.org.uk
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Andrews
authors.forename: Woolf T
authors.initials: WT
authors.lastname: Walker
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
authors.forename: Paul T
authors.initials: PT
authors.lastname: Heath
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Collinson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Snape
authors.forename: Saul N
authors.initials: SN
authors.lastname: Faust
authors.forename: Pauline A
authors.initials: PA
authors.lastname: Waight
authors.forename: Katja
authors.initials: K
authors.lastname: Hoschler
authors.forename: Liz
authors.initials: L
authors.lastname: Sheasby
authors.forename: Claire
authors.initials: C
authors.lastname: Waddington
authors.forename: Simon
authors.initials: S
authors.lastname: Kerridge
authors.forename: Jeremy
authors.initials: J
authors.lastname: Chalk
authors.forename: Amanda
authors.initials: A
authors.lastname: Reiner
authors.forename: Tessa
authors.initials: T
authors.lastname: John
authors.forename: Margaret
authors.initials: M
authors.lastname: Fletcher
authors.forename: Ruth
authors.initials: R
authors.lastname: Allen
authors.forename: Natalie
authors.initials: N
authors.lastname: Fineman
authors.forename: Su
authors.initials: S
authors.lastname: Wilkins
authors.forename: Michelle
authors.initials: M
authors.lastname: Casey
authors.forename: Louise
authors.initials: L
authors.lastname: Michaelis
authors.forename: Clarissa
authors.initials: C
authors.lastname: Oeser
authors.forename: Ifeanyichukwu
authors.initials: I
authors.lastname: Okike
authors.forename: Shamez
authors.initials: S
authors.lastname: Ladhani
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; 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 / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage* / Q000009:adverse effects; D013185:Squalene / Q000008:administration & dosage* / Q000009:adverse effects; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D015164:Vaccines, Inactivated; D022223:Vaccines, Subunit; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol