Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae:: a randomised double-blind efficacy study
Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae:: a randomised double-blind efficacy study
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DOI：
10.1016/s0140-6736(06)68304-9
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发表时间：
2006-03-04
期刊：
影响因子：
168.9
通讯作者：
Schuerman, L
中科院分区：
文献类型：
--
作者：
Prymula, R;Peeters, P;Schuerman, L
背景急性中耳炎是儿童最常见的感染性疾病之一。这项研究评估了一种新型疫苗的预防急性中耳炎的效果，该疫苗含有11种不同肺炎链球菌血清型的多糖，每个血清型都与流感嗜血杆菌衍生蛋白D结合，预防急性中耳炎。方法4968名婴儿在3、4、5和12-15个月时随机分配接种肺炎球菌D蛋白结合物或甲型肝炎疫苗，并进行随访，直到第二年结束。对于鼓膜异常或有中耳积液，并有两个预先确定的临床症状的儿童，取中耳液进行细菌培养和血清分型。主要终点是对疫苗肺炎球菌血清型引起的第一次急性中耳炎的保护效果。从第三次注射后2周到24-27个月龄，蛋白D结合物组(n=2455)和对照组(n=2452)分别记录了333例急性中耳炎和499例急性中耳炎的临床发作，急性中耳炎的总发病率显著降低(33.6%[95%CI 20.8-44.3])。肺炎球菌疫苗血清型引起的急性中耳炎发作的疫苗有效率为52.6%[35.0-65.5]，任何一次发作均为57.6%[41.4-69.3]。对非分型H型流感引起的急性中耳炎发作也显示出疗效(35.3%[1.8-57.4])。该疫苗降低了疫苗相关交叉反应肺炎球菌血清型的感染频率65.5%，但没有显著改变其他非疫苗血清型引起的发病次数。解释这些结果证实，使用流感嗜血杆菌衍生蛋白D作为肺炎球菌多糖的载体蛋白不仅可以预防肺炎球菌中耳炎，而且可以预防非分型流感嗜血杆菌引起的急性中耳炎。这种方法是否也能改善对下呼吸道感染的保护，值得进一步研究。
Background Acute otitis media is one of the most commonly-diagnosed childhood infections. This study assessed the efficacy of a novel vaccine that contained polysaccharides from 11 different Streptococcus pneumoniae serotypes each conjugated to Haemophilus influenzae-derived protein D in prevention of acute otitis media.Methods 4968 infants were randomly assigned to receive either pneumococcal protein D conjugate or hepatitis A vaccine at the ages of 3, 4, 5, and 12-15 months and were followed-up until the end of the second year of life. Middle-ear fluid was obtained for bacteriological culture and serotyping in children who presented with abnormal tympanic membrane or presence of middle-ear effusion, plus two predefined clinical symptoms. The primary endpoint was protective efficacy against the first episode of acute otitis media caused by vaccine pneumococcal serotypes. Analysis was per protocol.Findings From 2 weeks after the third dose to 24-27 months of age, 333 clinical episodes of acute otitis media were recorded in the protein D conjugate group (n=2455) and 499 in the control group (n=2452), giving a significant (33.6% [95% CI 20.8-44.3]) reduction in the overall incidence of acute otitis media. Vaccine efficacy was shown for episodes of acute otitis media caused by pneumococcal vaccine serotypes (52.6% [35.0-65.5] for the first episode and 57.6% [41.4-69.3] for any episode). Efficacy was also shown against episodes of acute otitis media caused by non-typable H influenzae (35.3% [1.8-57.4]). The vaccine reduced frequency of infection from vaccine-related cross-reactive pneumococcal serotypes by 65.5%, but did not significantly change the number of episodes caused by other non-vaccine serotypes.Interpretation These results confirm that using the H influenzae-derived protein D as a carrier protein for pneumococcal polysaccharides not only allowed protection against pneumococcal otitis, but also against acute otitis media due to non-typable H influenzae. Whether this approach would also allow improved protection against lower respiratory tract infections warrants further investigation.