Abstract
ABSTRACTWe investigated the role of AS03A (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.)
Highlights
We investigated the role of AS03A, an ␣-tocopherol oil-inwater emulsion-based adjuvant system, on the long-term persistence of humoral and cell-mediated immune responses to A(H1N1)pdm09 influenza vaccines
Previously, we presented the Hemagglutination inhibition (HI) antibody and CD4ϩ T-cell responses elicited by two doses of AS03-adjuvanted or nonadjuvanted A(H1N1)pdm09 influenza vaccine up to day 42 in two populations of adults Յ60 years of age [6]
While no intergroup statistical comparisons were performed, these data suggest that (i) two doses of adjuvanted vaccine (3.75 g HA) or nonadjuvanted vaccine at 15 g of HA but not at 3.75 g of HA elicited HI antibody responses persisting at levels meeting Committee for Human Medicinal Products (CHMP) criteria through month 12; (ii) advancing age and a history of seasonal influenza vaccination tended to reduce the HI antibody and memory B-cell responses, while such effects were less consistently observed for the CD4ϩ T-cell responses; and (iii) the use of AS03 may have enhanced the persistence of vaccine responses of both arms of the immune system, mitigating any potential negative effects of age and previous seasonal vaccination
Summary
We investigated the role of AS03A (here AS03), an ␣-tocopherol oil-inwater emulsion-based adjuvant system, on the long-term persistence of humoral and cell-mediated immune responses to A(H1N1)pdm influenza vaccines. Supplementing the earlier data, the present report describes the persistence of the vaccine-induced A(H1N1)pdm09-specific HI antibody T-cell and memory B-cell responses at 6 months (the expected transmission period for influenza virus during one season) and 12 months following the first dose in the same populations. These responses were evaluated overall and stratified by the participants’ previous receipt of seasonal influenza vaccination, their age, or both. We describe the vaccine safety data through the end of the study
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