title: Safety and immunogenicity of two different doses of a Vero cell-derived, whole virus clade 2 H5N1 (A/Indonesia/05/2005) influenza vaccine.
abstract: A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naïve subjects and evaluation of post-vaccination responsiveness. An open-label, randomized, phase I/II study therefore assessed the immunogenicity and safety of two different dose levels of an inactivated, non-adjuvanted, whole virus clade 2.1 (A/Indonesia/05/2005) H5N1 Vero cell-derived influenza vaccine in healthy adults (21-45 years) from a region where the virus has been circulating (Hong Kong) as well as Singapore. Subjects (N=110) were randomized 1:1 to receive two vaccinations with either 3.75 μg or 7.5 μg H5N1 haemagglutinin antigen 21 days apart. Safety, immunogenicity (microneutralization [MN] and single radial haemolysis [SRH] at baseline and post-vaccination) and cross-reactivity against a heterologous clade 1 strain (A/Vietnam/1203/2004) of the vaccine were assessed. Pre-existing immunity to the vaccine strain was 14% which is higher than previously reported for these regions. Two vaccinations with either vaccine formulation induced high seroprotection rates (MN titre ≥ 1:20) against the vaccine strain A/Indonesia/05/2005: 82.7% and 86.5% in the 3.75 μg and 7.5 μg dose groups. Seroconversion rates and fold increase exceeded the CPMP criterion of >40% and >2.5 for MN and SRH in both dose groups after the second vaccination, while the seroprotection rate in the 7.5 μg dose group determined by SRH was only marginally lower (69.2%) than the CPMP criterion of >70%. Thus, 11 of 12 CHMP criteria were fulfilled. A cross-reactive antibody response against the heterologous A/Vietnam/1203/2004 strain was demonstrated after the second vaccination (>21% by MN and ≥ 25% by SRH). Persistence of antibodies against the vaccine strain was also demonstrated 6 months after the first vaccination, indicating that a booster vaccination would be effective in those who have received two priming doses. No serious adverse events were reported. The H5N1 influenza vaccine against clade 2.1 strain A/Indonesia/05/2005 was well tolerated and immunogenic after two vaccinations, and induced a cross-neutralizing antibody response, with no dose effect.
authors.affiliation: National University Hospital, 5 Lower Kent Ridge Road, Singapore.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Tambyah
authors.forename: Annelies
authors.initials: A
authors.lastname: Wilder-Smith
authors.forename: Borislava G
authors.initials: BG
authors.lastname: Pavlova
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
authors.forename: Helen M L
authors.initials: HM
authors.lastname: Oh
authors.forename: David S
authors.initials: DS
authors.lastname: Hui
authors.forename: Kwok-yung
authors.initials: KY
authors.lastname: Yuen
authors.forename: Sandor
authors.initials: S
authors.lastname: Fritsch
authors.forename: Gerald
authors.initials: G
authors.lastname: Aichinger
authors.forename: Alexandra
authors.initials: A
authors.lastname: Loew-Baselli
authors.forename: Maikel
authors.initials: M
authors.lastname: van der Velden
authors.forename: Friedrich
authors.initials: F
authors.lastname: Maritsch
authors.forename: Otfried
authors.initials: O
authors.lastname: Kistner
authors.forename: Hartmut J
authors.initials: HJ
authors.lastname: Ehrlich
mesh_terms: D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D003429:Cross Reactions; D006723:Hong Kong; D006801:Humans; D007118:Immunoassay; D053124:Influenza A Virus, H5N1 Subtype / Q000254:growth & development / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008875:Middle Aged; D012846:Singapore; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*; D014709:Vero Cells
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines