CPC Clinic, Medipolis Medical Research Institute, Kagoshima, Japan.
Vaccine. 2012 Jul 13;30(33):5030-7. doi: 10.1016/j.vaccine.2012.03.053. Epub 2012 Apr 1.
Effective vaccination strategies are required to combat future influenza pandemics. Here we report the results of three independent clinical trials performed in Japan to assess the immunogenicity, tolerability and safety of varying doses of a cell culture-derived MF59(®)-adjuvanted A/H1N1 pandemic vaccine in healthy Japanese paediatric, adult and elderly subjects.
One hundred and twenty-three children (6 months-18 years), and 200 adults (19-60 years) were randomly assigned in a 1:1 ratio to receive two doses of vaccine containing either 7.5 μg antigen with a full (9.75 mg) adjuvant dose, or 3.75 μg antigen with a half (4.875 mg) adjuvant dose. One hundred elderly (≥ 61 years) subjects received only the low antigen/adjuvant vaccine formulation. Immunogenicity was assessed by haemagglutination inhibition assay at baseline and three weeks after the first and second vaccine doses on Days 22 and 43, respectively. Solicited and unsolicited adverse reactions were recorded for seven and 21 days post-immunization, respectively.
In adult and elderly subjects, a single low antigen/adjuvant dose vaccination was sufficient to meet all of the three European licensure criteria established for influenza vaccines. One high, or two low antigen/adjuvant dose vaccinations were required to meet the licensure criteria in paediatric subjects. Both vaccine formulations were well tolerated, with the majority of adverse reactions mild to moderate in severity. None of the five serious adverse events reported throughout the three trials were considered to be vaccine-related by the investigators.
The use of MF59 adjuvant allows for much reduced vaccine antigen content, and a single dose administration schedule in adults and the elderly. The production of pandemic vaccine using modern cell culture techniques is highly advantageous in terms of the quantity, quality, and rapidity of antigen production; these benefits, in combination with the use of MF59, maximize manufacturing capacity and global vaccine supply. These data support the suitability of the investigational vaccine for use in the Japanese paediatric, adult, and elderly populations.
为应对未来的流感大流行，需要制定有效的疫苗接种策略。本研究报告了在日本进行的三项独立临床试验的结果，旨在评估细胞培养衍生的 MF59（®）佐剂 A/H1N1 流感大流行疫苗在健康的日本儿童、成人和老年受试者中的免疫原性、耐受性和安全性。
123 名儿童（6 个月至 18 岁）和 200 名成年人（19-60 岁）以 1:1 的比例随机分配，接受两剂疫苗，其中一剂含有 7.5 μg 抗原和全剂量（9.75 mg）佐剂，另一剂含有 3.75 μg 抗原和半剂量（4.875 mg）佐剂。100 名老年人（≥61 岁）仅接受低抗原/佐剂疫苗制剂。在第一次和第二次疫苗接种后 3 周（分别为第 22 天和第 43 天）以及第 22 天和第 43 天，通过血凝抑制试验评估免疫原性。分别在接种后 7 天和 21 天内记录有症状和无症状不良反应。
在成年和老年受试者中，单次低抗原/佐剂剂量接种足以满足欧洲为流感疫苗制定的三个许可标准。在儿童受试者中，需要一剂高剂量或两剂低抗原/佐剂剂量接种才能满足许可标准。两种疫苗制剂均具有良好的耐受性，大多数不良反应的严重程度为轻度至中度。在整个三项试验中报告的五例严重不良事件中，调查人员认为没有一例与疫苗有关。
使用 MF59 佐剂可使疫苗抗原含量降低很多，并使成人和老年人的疫苗接种剂量减少为单剂。使用现代细胞培养技术生产大流行疫苗在抗原产量的数量、质量和速度方面具有很高的优势；这些优势，结合 MF59 的使用，最大限度地提高了生产能力和全球疫苗供应。这些数据支持该研究性疫苗在日本儿童、成人和老年人群中的适用性。
