Yasuda Clinic, Minami-ku, Kyoto, Japan.
Adv Ther. 2010 Jul;27(7):444-57. doi: 10.1007/s12325-010-0043-4. Epub 2010 Jun 25.
The substantial pandemic (A/H1N1v) influenza disease burden in children highlights the need for effective vaccination. We report the results of modern cell culture technology, lower doses of antigen, and different doses of MF59(R) adjuvant (Novartis Vaccines, Marburg, Germany), on the immunogenicity and safety profile in a healthy Japanese pediatric population.
A total of 123 children from 6 months to 19 years of age were randomly assigned in a 1:1 ratio to receive, at 21-day intervals, two doses of either 3.75 microg antigen with 50% of the standard MF59 dose (group A) or 7.5 microg antigen and 100% standard MF59 dose (group B). Antibody levels were measured by hemagglutinin inhibition (HI) and microneutralization assays on day 1 and on days 22 and 43 (3 weeks after the first and second vaccinations, respectively). Solicited adverse events were reported for 7 days after each injection and spontaneous events were reported throughout the study period.
At 3 weeks after the first vaccination, seroprotective HI antibodies (titers >or=40) were observed in 56% and 78% of subjects from groups A and B, respectively; 100% in both groups exhibited HI titers >or=40 after the second dose. The reactogenicity profile was acceptable, with local and systemic reactions described as mainly mild to moderate in severity. Five serious adverse events were reported, but none related to the study vaccine.
One dose of cell culture-derived A/H1N1v vaccine containing 7.5 microg antigen with the full MF59 adjuvant dose was immunogenic and well tolerated in healthy Japanese children, meeting all three European Union Committee for Medicinal Products for Human Use (EU CHMP) licensure criteria. Two doses of 3.75 microg antigen with 50% of the standard MF59 dose fulfilled these licensure criteria.
大流行（A/H1N1v）流感疾病在儿童中的大量负担突出了有效疫苗接种的必要性。我们报告了现代细胞培养技术、抗原低剂量和不同剂量 MF59（R）佐剂（诺华疫苗，马尔堡，德国）的结果，这些结果在健康的日本儿科人群中具有免疫原性和安全性。
总共 123 名 6 个月至 19 岁的儿童随机以 1:1 的比例分为两组，每组在 21 天的间隔内接受两次剂量的抗原，分别为 3.75 微克抗原和 50%的标准 MF59 剂量（A 组）或 7.5 微克抗原和 100%标准 MF59 剂量（B 组）。在第 1 天和第 22 天和第 43 天（分别为第一次和第二次接种后 3 周），通过血凝抑制（HI）和微量中和试验测量抗体水平。每次注射后 7 天报告应征不良反应，整个研究期间报告自发不良反应。
第一次接种后 3 周，A 组和 B 组分别有 56%和 78%的受试者产生保护性 HI 抗体（滴度>或=40）；两组均有 100%的 HI 滴度>或=40 。反应原性特征是可以接受的，局部和全身反应主要为轻度至中度。报告了 5 例严重不良事件，但均与研究疫苗无关。
在健康的日本儿童中，一剂含有 7.5 微克抗原和完整 MF59 佐剂剂量的细胞培养衍生的 A/H1N1v 疫苗具有免疫原性和良好的耐受性，符合欧盟药品管理局（EU CHMP）的所有三个许可标准。两剂 3.75 微克抗原和 50%标准 MF59 剂量符合这些许可标准。
