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In this study we describe the immunogenicity results from a subset of older people (N = 5187) who participated in a Phase 3 randomized, observer-blinded trial of AS03-TIV versus TIV (Fluarix™) (ClinicalTrials.gov, NCT00753272). Participants received one dose of AS03-TIV or TIV in each study year and antibody titers against the vaccine strains were assessed using hemagglutination-inhibition (HI) assay at 21 d and 180 d post-vaccination in each vaccine group in the 2008/09 (Year 1) and 2009/10 (Year 2) influenza seasons. Manufacturing consistency of 3 lots of AS03-TIV for HI antibody responses in Year 1 was a co-primary objective. In a post-hoc analysis, a statistical regression model included 4830 subjects in whom immunogenicity and laboratory-confirmed attack rate data were available; the analysis was performed to assess HI antibody titers against A/H3N2 as a correlate of protection for laboratory-confirmed A/H3N2 influenza. AS03-TIV and TIV elicited strong HI antibody responses against each vaccine strain 21 d post-vaccination in both years. The manufacturing consistency of 3 lots of AS03-TIV was demonstrated. In both years and each vaccine group, HI antibody responses were lower for A/H1N1 than the other vaccine strains. Day 180 seroconversion rates (proportion with ≥4-fold increase in titer compared with pre-vaccination titer) in Year 1 in the AS03-TIV and TIV groups, respectively, were 87.7% and 74.1% for A/H3N2, 69.7% and 59.6% for influenza B, and 58.3% and 47.4% for A/H1N1. The post-hoc statistical model based on A/H3N2 attack rates and HI antibody titers estimated that a 4-fold increase in post-vaccination titers against A/H3N2 was associated with a 2-fold decrease in the odds of A/H3N2 infection.

Patient-reported outcomes (PROs) are particularly relevant in influenza vaccine trials in the elderly where reduction in symptom severity could prevent illness-related functional impairment.

Background: Improved influenza vaccines are needed to reduce influenza-associated complications in older adults. The aim of this study was to identify the optimal formulation of adjuvanted seasonal influenza vaccine for use in elderly people. Methods: This observer-blind, randomized study assessed the optimal formulation of adjuvanted seasonal influenza vaccine based on immunogenicity and safety in participants aged >= 65 years. Participants were randomized (similar to 200 per group) to receive one dose of non-adjuvanted vaccine or one of eight formulations of vaccine formulated with a squalene and tocopherol oil-in-water emulsion-based Adjuvant System (AS03(C), AS03(B) or AS03(A), with 2.97, 5.93 and 11.86 mg tocopherol, respectively) together with the immunostimulant monophosphoryl lipid A (MPL, doses of 0, 25 or 50 mg). Hemagglutination-inhibition (HI) antibody responses and T-cell responses were assessed on Day 0 and 21 days post-vaccination. The ratio of HI-based geometric mean titers in adjuvanted versus non-adjuvanted vaccine groups were calculated and the lower limit of the 90% confidence interval was transformed into a desirability index (a value between 0 and 1) in an experimental domain for each vaccine strain, and plotted in relation to the AS03 and MPL dose combination in the formulation. This model was used to assess the optimal formulation based on HI antibody titers. Reactogenicity and safety were also assessed. The immunogenicity and safety analyses were used to evaluate the optimal formulation of adjuvanted vaccine. Results: In the HI antibody-based model, an AS03 dose-response was evident; responses against the A/H1N1 and A/H3N2 strains were higher for all adjuvanted formulations versus non-adjuvanted vaccine, and for the AS03(A)-MPL25, AS03(B)-MPL25 and AS03(B)-MPL50 formulations against the B strain. Modelling using more stringent criteria (post hoc) showed a clear dose-range effect for the AS03 component against all strains, whereas MPL show

During the 2009-2010 Northern Hemisphere influenza season, both seasonal and pandemic influenza vaccines were expected to be administered to elderly people, which is an important target group for influenza vaccination. Two multicentre randomised clinical studies were conducted in participants aged >= 61 years to assess the immunogenicity and reactogenicity following vaccination with two doses of an AS03-adjuvanted A(H1N1)pmd09 vaccine when either sequentially administered (21 days before first dose [N = 73] or 21 days after second dose [N = 72]) or co-administered (first dose [N = 84] or second dose [N = 84]) with a licensed trivalent seasonal influenza vaccine (TIV). Overall, 313 participants from 2 centres in Sweden (ClinicalTrials.gov, NCT00968890) and 6 centres in Germany (NCT00971425) were randomised to one of the four treatment groups. The AS03-adjuvanted A(H1N1)pmd09 vaccine elicited a good immune response against A(H1N1)pmd09-like virus in all treatment groups after the first and second dose, meeting and exceeding the European licensing criteria for pandemic influenza vaccines. After one dose of the AS03-adjuvanted A(H1N1)pmd09 vaccine, haemagglutination inhibition seroconversion rates ranged from 85% (95% confidence interval: 74-93%) to 93% (85-97%), seroprotection rates from 87% (76-94%) to 96% (90-99%) and geometric mean fold rise from 15 (11-19) to 20 (16-25). The haemagglutination inhibition immune responses to the AS03-adjuvanted A(H1N1)pmd09 vaccine seemed lower when TIV was administered 3 weeks before, while immune responses to TIV seemed not affected by either vaccination schedule. Solicited symptoms were more frequently reported following administration of the AS03-adjuvanted A(H1N1)pmd09 vaccine compared to TIV, but these were mainly mild to moderate in intensity and transient in the four treatment groups. These results suggest that sequential or co-administration of the AS03-adjuvanted A(H1N1)pmd09 vaccine and TIV induced a good immune respons, De två första författarna delar förstaförfattarskapet.