Long-Term Persistence of Cell-Mediated and Humoral Responses to A(H1N1)pdm09 Influenza Virus Vaccines and the Role of the AS03 Adjuvant System in Adults during Two Randomized Controlled Trials.

We investigated the role of AS03_A (here AS03), an α-tocopherol oil-in-water emulsion-based adjuvant system, on the long-term persistence of humoral and cell-mediated immune responses to A(H1N1)pdm09 influenza vaccines. In two studies, a total of 261 healthy adults (≤60 years old) were randomized to receive two doses of AS03-adjuvanted vaccine containing 3.75 μg of hemagglutinin (HA) or nonadjuvanted vaccine containing 15 μg of hemagglutinin (in study A) or 3.75 μg of hemagglutinin (in study B) 21 days apart. Hemagglutination inhibition (HI) antibody, memory B-cell, and CD4⁺/CD8⁺ T-cell responses were characterized up to 1 year following dose 1. We also assessed the effects of age and seasonal influenza vaccination history. AS03-adjuvanted (3.75 μg HA) vaccine and nonadjuvanted vaccine at 15 μg but not at 3.75 μg HA elicited HI antibody responses persisting at levels that continued to meet European licensure criteria through month 12. At month 12, the geometric mean titer for AS03-adjuvanted vaccine was similar to that for nonadjuvanted (15-μg) vaccine in study A (1:86 and 1:88, respectively) and higher than that for nonadjuvanted (3.75-μg) vaccine in study B (1:77 and 1:35, respectively). A(H1N1)pdm09-specific CD4⁺ T-cell and B-cell responses were stronger in AS03-adjuvanted groups and persisted only in these groups for 12 months at levels exceeding prevaccination frequencies. Advancing age and a seasonal vaccination history tended to reduce HI antibody and memory B-cell responses and, albeit less consistently, CD4⁺ T-cell responses. Thus, AS03 seemed to enhance the persistence of humoral and cell-mediated responses to A(H1N1)pdm09 vaccine, allowing for antigen sparing and mitigating potential negative effects of age and previous seasonal vaccination. (These studies have been registered at ClinicalTrials.gov under registration no. NCT00968539 and NCT00989287.).