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目的确定单针剂C群脑膜炎球菌(Men C)结合疫苗在婴儿12月龄接种加强剂量疫苗后的免疫原性是否不比双针剂疫苗免疫原性差。设计2010年7月-2013年8月进行第Ⅳ阶段的开放标签随机对照试验。试验地点4个试验中心位于英国,1个试验中心位于马耳他。参与者对年龄在6~12周的健康婴儿进行随访,直到年龄满24个月为止。干预在试验的启动阶段,509例婴儿按照10∶10∶7∶4的比例,随机分为4组:第1组(单针剂Men C-CRM组)在3个月时接种单针剂Men C-CRM;第2组(双针剂Men C-CRM组)在3个月和4个月时接种Men C-CRM,共接种2针剂;第3组在3个月时接种单针剂Men C-多糖-破伤风类毒素(TT);第4组不接种Men C。所有婴儿12月龄时,接种b型流感嗜血杆菌(Hib)-Men C-TT疫苗。所有婴儿接种全国范围内常规推荐的疫苗。分别在5、12、13、24月龄时留取血样。主要测量指标接种Hib-Men C-TT疫苗后1个月,利用家兔补体进行Men C血清抗体杀菌活性的检测(r SBA)。如果单针剂Men C-CRM组和双针剂Men C-CRM组的平均log10 Men C r SBA之差的95%可信区间(95%CI)下限>-0.35,则符合非劣效性。结果单针剂Men C-CRM组婴儿12月龄接种加强剂量的Hib-Men C-TT疫苗后,其Men C r SBA几何平均滴度并不次于双针剂Men C-CRM组婴儿〔660,95%CI(498,876)与295,95%CI(220,398)〕,单针剂Men C-CRM组和双针剂Men C-CRM组的平均log10 Men C r SBA之差为0.35,95%CI(0.17,0.53),显示了单针剂接种相对于双针剂接种的优越性。对两组存在的差异进行探索显示,在接种Hib-Men C-TT疫苗1个月后,>96%的之前接种过Men C的参加者Men C r SBA≥1∶8,而之前没有接种过Men C的参加者,Men C r SBA≥1∶8的比例只有83%。在接种单针剂Men C-CRM后,再接种Hib-Men C-TT疫苗的儿童,其Men C r SBA几何平均滴度要显著高于接种双针剂Men C-CRM儿童。然而,只有采用Men C-TT进行首次接种,Hib-Men C-TT疫苗加强剂量诱导的Men C杀菌抗体才能保持到24月龄。结论双针剂Men C的接种规划可以减少到单针剂,而不影响抗体滴度。之前接种过单针剂Men C-TT疫苗的婴儿,在接种加强剂量Hib-Men C-TT疫苗后,与仅接种单针剂Men C-CRM或双针剂Men C-CRM的婴儿相比,可产生更稳健的抗体反应。由于Men C抗体滴度的快速下降,那些只在学步期接种疫苗的儿童,将来仍然需要依赖群体接种,以保护婴幼儿不受脑膜炎影响。
OBJECTIVE: To determine if the immunogenicity of a single dose of the Men C conjugate vaccine at 12 months of age in vaccinated booster doses of the vaccine is no worse than that of the two-dose vaccine. Design July 2010 - August 2013 Phase IV open-label randomized controlled trials. The test sites are four test centers in the United Kingdom and one in Malta. Participants followed up healthy infants aged 6-12 weeks until they reached 24 months of age. Intervention At the start-up phase of the trial, 509 infants were randomized into 4 groups at a ratio of 10:10:7:4: Group 1 (single-dose Men C-CRM group) were given a single dose of Men C- CRM; Group 2 (Men C-CRM group) were inoculated with 2 doses of Men C-CRM at 3 months and 4 months; Group 3 were given a single dose of Men C-CRM at 3 months Tetanus toxoid (TT); Group 4 did not inoculate Men C. All infants were vaccinated with Haemophilus influenzae type b (Hib) -Men C-TT at 12 months of age. All infants are vaccinated regularly across the country. Blood samples were taken at 5, 12, 13, and 24 months of age respectively. MAIN MEASUREMENTS One month after inoculation of the Hib-Men C-TT vaccine, rabbit C complement antibody was used for the detection of MenC serum antibody bactericidal activity (r SBA). Noninferiority was demonstrated if the 95% confidence interval (95% CI) lower limit of> -0.35 between the mean log10 Men C r SBA for the single-dose Men C-CRM group and the dual-dose Men C-CRM group. Results The geometric mean titer of Men C r SBA was not inferior to that of double-dose Men C-CRM infants [12 months % CI (498,876) vs. 295,95% CI (220,398)], the difference between the mean log10 Men C r SBA for the single-dose Men C-CRM group and the double-dose Men C-CRM group was 0.35, 95% CI (0.17, 0.53 ), Shows the superiority of single inoculation versus double inoculation. An exploration of the differences between the two groups revealed that> 96% of Men C r SBA ≧ 1: 8 participants who had previously been vaccinated with Men C after 1 month of vaccination with Hib-Men C-TT had not previously been vaccinated Men C participants, Men C r SBA ≥ 1: 8 ratio was only 83%. Children who received the Hib-Men C-TT vaccine after the single-dose Men C-CRM inoculation had significantly higher geometric mean geometric mean Men C r SBA titers than inoculated double-dose Men C-CRM children. However, the dose-boosting Men C bactericidal antibody to Hib-Men C-TT vaccine was maintained to 24 months of age only with the first vaccination with Men C-TT. Conclusions The dual-dose Men C vaccination schedule can be reduced to single-shot without affecting antibody titers. Infants previously vaccinated with the single-dose Men C-TT vaccine developed more potent infants than those who received single-dose Men C-CRM or dual-dose Men C-CRM after boosting doses of the Hib-Men C-TT vaccine Robust antibody response. Due to the rapid drop in Men C antibody titers, those who vaccinate only during toddlers will still need to rely on group vaccination in the future to protect their babies from meningitis.