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, 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 (NCT00968539/NCT00989287), a total of 261 healthy adults (age ≤60 years) were randomized to receive two doses of AS03-adjuvanted vaccine containing 3.75 μg hemagglutinin, or non-adjuvanted vaccine containing 15 μg hemagglutinin (in Study A) or 3.75 μg 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) vaccine and non-adjuvanted vaccine at 15 μg but not at 3.75 μg 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 non-adjuvanted (15-μg) vaccine in Study A (1:86 and 1:88, respectively) and higher than that for non-adjuvanted (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 higher in AS03-adjuvanted groups and persisted only in these groups for 12 months at levels exceeding pre-vaccination 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.