title: Priming with AS03 A-adjuvanted H5N1 influenza vaccine improves the kinetics, magnitude and durability of the immune response after a heterologous booster vaccination: an open non-randomised extension of a double-blind randomised primary study.
abstract: An influenza vaccine with cross-immunogenic potential could play a key role in pandemic mitigation by promoting a rapid immune response to infection and/or subsequent vaccination with strains drifted from the primary vaccine strain. Here we assess the role of AS03(A) (an oil-in-water emulsion based Adjuvant System containing tocopherol) in this prime-boost concept using H5N1 as a model shift influenza antigen. In this open, non-randomised study (NCT00506350; an extension of an earlier randomised study) we assessed immunogenicity in nine groups of 35-50 volunteers aged 19-61 years following administration of AS03(A)-adjuvanted split-virion H5N1 vaccine containing 3.75mug of haemagglutinin (HA) from the A/Indonesia/5/2005(IBCDC-RG2) clade 2.1 strain. A single booster dose of vaccine was administered to four groups primed 14 months previously with different HA levels of AS03(A)-adjuvanted clade 1 A/Vietnam/1194/2004 H5N1 vaccine. Two booster doses (given 21 days apart) were administered to four groups primed 14 months previously with different HA levels of non-adjuvanted A/Vietnam/1194/2004 H5N1 vaccine and also to a control group of un-primed subjects. In individuals primed 14 months earlier with AS03(A)-adjuvanted A/Vietnam/1194/2004 vaccines, a single booster dose of AS03(A)-adjuvanted A/Indonesia/5/2005 induced rapid immune responses (licensure criteria met in 7-14 days) comparable to that observed in the un-primed control group following two doses of adjuvanted vaccine. In contrast, individuals primed with non-adjuvanted formulations exhibited minimal immune responses which, even after two doses, were unexpectedly much lower than that observed in un-primed subjects. AS03(A) enhances the initial priming effect of pandemic influenza vaccination enabling a rapid humoral response to single dose boosting with a heterologous strain at 14 months. In contrast, priming without adjuvant appears to inhibit the response to subsequent vaccination with a heterologous strain. These findings should guide the development of vaccines to combat the present influenza A/H1N1 pandemic.
authors.affiliation: Center for Vaccinology, Ghent University and Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Isabel
authors.initials: I
authors.lastname: Leroux-Roels
authors.forename: François
authors.initials: F
authors.lastname: Roman
authors.forename: Sheron
authors.initials: S
authors.lastname: Forgus
authors.forename: Cathy
authors.initials: C
authors.lastname: Maes
authors.forename: Fien
authors.initials: F
authors.lastname: De Boever
authors.forename: Mamadou
authors.initials: M
authors.lastname: Dramé
authors.forename: Paul
authors.initials: P
authors.lastname: Gillard
authors.forename: Robbert
authors.initials: R
authors.lastname: van der Most
authors.forename: Marcelle
authors.initials: M
authors.lastname: Van Mechelen
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hanon
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D018849:Controlled Clinical Trials as Topic; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006389:Hemagglutinins, Viral / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007214:Indonesia; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014744:Vietnam; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines; D022223:Vaccines, Subunit; C458881:hemagglutinin fusogenic peptide, influenza virus