Priming for Pandemic Influenza: Antigen-sparing MF59™-adjuvanted A/H5N1 Vaccine Induces Immunological Memory and Shows Cross-Reactive Potential in Adults Including the Elderly

Background: Priming against strains with pandemic potential, such as H5N1, with vaccines that induce immunological memory and cross-reactivity, may form the first line of defence against a pandemic flu. Safe and effective H5N1 vaccines, particularly those that can induce cross-reactive immunity, are urgently needed for prepandemic vaccination strategies. Methods: Healthy adults aged 18–60 years (n = 313) and elderly aged >60 years (n = 173) received two injections (1:1 ratio), 3 weeks apart, and a six-month booster dose, of a subunit MF59-adjuvanted H5N1 (A/Vietnam/1194/2004) influenza (clade 1) vaccine containing either 7.5 μg or 15 μg hemagglutinin. All participants were followed for safety assessments. Blood samples were taken before each vaccination, and again three weeks and six months after each vaccination. Serum H5N1 antibody titres were assessed by single radial hemolysis and microneutralisation assays. Findings: Mild pain at the injection site was the most common reaction overall and decreased with subsequent dosing. The humoral immune response to 7.5 μg vaccine was non-inferior to that of 15 μg. Seroprotection rates after the second vaccination ranged from 80% to 86% as measured by SRH and 76% to 85% as measured by MN assays across vaccine dose and age strata. After the six-month booster, seroprotection rates, as measured by SRH, increased in adults and elderly in the 7.5 μg group from 19% and 22% at baseline (pre-booster) to 90% and 84%, respectively, three weeks later, and in the 15 μg group from 25% and 64% at baseline for adults and elderly, respectively, to 91% and 88%. Heterologous immune response against the A/H5N1/turkey/Turkey/05 strain was detectable after the second vaccination and the booster vaccination, with seroprotection rate of 57–76% and 78–88% after the second and third dose respectively. Interpretations: Both formulations were well tolerated and equivalent. The 7.5 μg met all three SRH criteria for pandemic vaccines licensure in the EU in both adult and elderly participants. The cross-clade immune response suggests that this vaccine adjuvanted with MF 59 is appropriate for H5N1 prepandemic vaccination programs.