Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
J Formos Med Assoc. 2012 Jun;111(6):333-9. doi: 10.1016/j.jfma.2011.02.006. Epub 2012 Apr 20.
BACKGROUND/PURPOSE: This study evaluated the immune response elicited by two formulations of an AS03(A)-adjuvanted H5N1 A/Indonesia/05/2005 prepandemic influenza vaccine, developed using manufacturing processes with or without thiomersal. In addition, it also evaluated compliance to the Centre for Biologics Evaluation and Research and Committee for Medicinal Products for Human Use (CHMP) immunogenicity guidance criteria for pandemic influenza vaccines in adults.
This phase III, observer-blind, randomized study (NCT00812981) enrolled 320 subjects aged 18-60 years into two groups to receive, 21 days apart, two doses of the formulation manufactured using either the thiomersal-containing process (Group TC) or the thiomersal-free process (Group TF). Blood samples collected before vaccination, 21 days after the second vaccine dose, and 6 months following the first vaccine dose (Days 0, 42, and 180) were analysed using a hemagglutination inhibition (HI) assay. Safety assessments were made for the entire study period.
Twenty-one days after the second dose of vaccine, both groups met the CHMP criteria for vaccine-homologous HI response (seroprotection rates/seroconversion rates ≥ 98.7%, seroconversion factor ≥ 121.9) and also for a heterologous HI response against the A/Vietnam/1194/2004 strain (seroprotection rates/seroconversion rates ≥ 81.3%, seroconversion factor ≥ 10.8). Six months after the first dose of vaccine, a marked persistence of the vaccine-homologous HI response was observed that still met one or more CHMP criteria. Pain at the injection site (Group TF 95%, Group TC 91.8%) and myalgia (Group TF 68.8%, Group TC 63.5%) were the most frequently recorded solicited symptoms. Overall, both formulations had a clinically acceptable safety profile.
Administration of two doses of the AS03(A)-adjuvanted H5N1 prepandemic influenza vaccine was found to be highly immunogenic in adults with a clinically acceptable safety profile. The ability to confer cross-clade protective immunity makes it a suitable option for mitigation of the morbidity and mortality of outbreaks and pandemics due to H5N1 and drifted strains.
背景/目的：本研究评估了两种 AS03(A) 佐剂 H5N1 A/印度尼西亚/05/2005 大流行前流感疫苗制剂引起的免疫应答，这两种疫苗制剂分别使用含有硫柳汞和不含有硫柳汞的制造工艺生产。此外，还评估了其在成人中的大流行流感疫苗的符合中心生物制品评价和研究中心和人用药品委员会（CHMP）免疫原性指导标准的情况。
这是一项 III 期、观察者盲法、随机研究（NCT00812981），将 320 名年龄在 18-60 岁的受试者分为两组，间隔 21 天分别接受两种制剂的两剂疫苗，一种制剂使用含有硫柳汞的工艺（TC 组），另一种制剂使用不含硫柳汞的工艺（TF 组）。在接种前（第 0 天）、第二次疫苗接种后 21 天（第 42 天）和第一次疫苗接种后 6 个月（第 180 天）采集血样，采用血凝抑制（HI）试验进行分析。整个研究期间均进行安全性评估。
第二次疫苗接种后 21 天，两组均符合 CHMP 关于疫苗同源 HI 应答（血清保护率/血清转化率≥98.7%，血清转化率≥121.9）和对 A/Vietnam/1194/2004 株的异源 HI 应答（血清保护率/血清转化率≥81.3%，血清转化率≥10.8）的标准。第一次疫苗接种后 6 个月，观察到疫苗同源 HI 应答明显持续，仍符合一个或多个 CHMP 标准。注射部位疼痛（TF 组 95%，TC 组 91.8%）和肌痛（TF 组 68.8%，TC 组 63.5%）是最常记录的局部症状。总的来说，两种制剂的安全性均具有临床可接受性。
在成人中，两次接种 AS03(A) 佐剂 H5N1 大流行前流感疫苗具有高度的免疫原性，安全性具有临床可接受性。该疫苗能够提供跨属保护免疫，是减轻 H5N1 和漂移株引起的发病率和死亡率的大流行的一种合适选择。
