Gillard Paul, Giet Didier, Heijmans Stéphane, Dramé Mamadou, Walravens Karl, Roman François
GSK Vaccines, Wavre, Belgium.
Trials. 2014 Oct 29;15:419. doi: 10.1186/1745-6215-15-419.
Older individuals often have a reduced immune response to influenza vaccination, which might be improved by administering a higher vaccine dose. We compared the immune response to two single doses of the AS03A-adjuvanted H5N1 pandemic vaccine (3.75 μg hemagglutinin of A/Vietnam/1194/2004) with that of two double vaccine doses (7.5 μg hemagglutinin) in adults aged ≥61 years. Here we report the 2-year persistence of the humoral and cellular immune response.
In this phase II, open-label study, healthy participants aged 61 to 88 years (median 68 years) were randomised (3:1:3:1) to receive two single doses of the AS03A-adjuvanted vaccine (1xH5N1-AS) or the non-adjuvanted vaccine (1xH5N1), or two double doses of the AS03A-adjuvanted vaccine (2xH5N1-AS) or the non-adjuvanted vaccine (2xH5N1), 21 days apart. Serum haemagglutination inhibition antibodies and cellular immune responses against A/Vietnam/1194/2004 were measured in all groups at months 12 and 24; neutralising antibodies were assessed in a subset of the adjuvanted groups. Serious adverse events and adverse events of specific interest were recorded.
At month 24, haemagglutination inhibition antibody seroprotection rates were 37.2% (95% CI 27.0% to 48.3%) for 1xH5N1-AS, 30.9% (95% CI 21.1% to 42.1%) for 2xH5N1-AS, 16.2% (95% CI 6.2% to 32.0%) for 1xH5N1, and 8.3% (95% CI 1.0% to 27.0%) for 2xH5N1. Haemagglutination inhibition antibody geometric mean titres were 17.6 (95% CI 13.7 to 22.5) for 1xH5N1-AS, 18.4 (95% CI 14.2 to 23.8) for 2xH5N1-AS, 12.3 (95% CI 8.9 to 16.9) for 1xH5N1 and 9.8 (95% CI 6.7 to 14.4) for 2xH5N1. The median frequency of antigen-specific CD4+ T cells per 106 T cells (25th quartile; 75th quartile) was 852 (482; 1477) for 1xH5N1-AS, 1147 (662; 1698) for 2xH5N1-AS, 556 (343; 749) for 1x-H5N1 and 673 (465; 1497) for 2xH5N1. Neutralising antibody geometric mean titres were 391.0 (95% CI 295.5 to 517.5) in the 1xH5N1-AS group and 382.8 (95% CI 317.4 to 461.6) in the 2xH5N1-AS group.
Antibody levels declined substantially in all groups. Seroprotection rates, geometric mean titres for haemagglutination inhibition antibodies, and CD4+ T-cell responses tended to be higher in the AS03A-adjuvanted groups. There was no clear benefit, in terms of long-term persistence of the immune response, of doubling the dose of the adjuvanted vaccine. No safety concern was observed up to 24 months post-primary vaccination.
NCT00397215 (7 November 2006).
老年人对流感疫苗的免疫反应通常会降低，增加疫苗剂量可能会改善这种情况。我们比较了≥61岁成年人中，两剂单剂量AS03A佐剂H5N1大流行疫苗（3.75μg A/越南/1194/2004血凝素）与两剂双剂量疫苗（7.5μg血凝素）的免疫反应。在此，我们报告体液和细胞免疫反应的2年持续性。
在这项II期开放标签研究中，61至88岁（中位年龄68岁）的健康参与者被随机分组（3:1:3:1），分别接受两剂单剂量AS03A佐剂疫苗（1xH5N1-AS）或无佐剂疫苗（1xH5N1），或两剂双剂量AS03A佐剂疫苗（2xH5N1-AS）或无佐剂疫苗（2xH5N1），间隔21天。在第12个月和第24个月时，对所有组测量血清血凝抑制抗体以及针对A/越南/1194/2004的细胞免疫反应；在部分佐剂组中评估中和抗体。记录严重不良事件和特定关注的不良事件。
在第24个月时，1xH5N1-AS组的血凝抑制抗体血清保护率为37.2%（95%CI 27.0%至48.3%），2xH5N1-AS组为30.9%（95%CI 21.1%至42.1%），1xH5N1组为16.2%（95%CI 6.2%至32.0%），2xH5N1组为8.3%（95%CI 1.0%至27.0%）。1xH5N1-AS组血凝抑制抗体几何平均滴度为17.6（95%CI 13.7至22.5），2xH5N1-AS组为18.4（95%CI 14.2至23.8），1xH5N1组为12.3（95%CI 8.9至16.9），2xH5N1组为9.8（95%CI 6.7至14.4）。每106个T细胞中抗原特异性CD4+T细胞的中位频率（第25四分位数；第75四分位数），1xH5N1-AS组为852（482；1477），2xH5N1-AS组为1147（662；1698），1x-H5N1组为556（343；749），2xH5N1组为673（465；1497）。1xH5N1-AS组中和抗体几何平均滴度为391.0（95%CI 295.5至517.5），2xH5N1-AS组为382.8（95%CI 317.4至461.6）。
所有组的抗体水平均大幅下降。AS03A佐剂组的血清保护率、血凝抑制抗体几何平均滴度和CD4+T细胞反应往往更高。就免疫反应的长期持续性而言，将佐剂疫苗剂量加倍并无明显益处。初次接种疫苗后至24个月未观察到安全问题。
NCT00397215（2006年11月7日）
