Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults
Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults
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DOI：
10.1016/s0140-6736(96)06255-1
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发表时间：
1997-01-18
期刊：
影响因子：
168.9
通讯作者：
Robbins, JB
中科院分区：
文献类型：
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作者：
Cohen, D;Ashkenazi, S;Robbins, JB
背景：这项双盲随机疫苗对照试验的目的是评估由宋内氏志贺氏菌O特异性多糖与铜绿假单胞菌重组外蛋白A结合的结合疫苗(S松内-repa)和口服减毒大肠杆菌/S福氏2a(EcSf2a-2)混合疫苗在以色列高危新兵中的有效性。我们在这里报告了我们关于S松内-REPA疗效的初步发现；我们没有足够的病例来评估ECSF2a-2的疗效。我们从七个不同的战地(A-G组)招募了1446名士兵。随机分为S松内-REPA 1针加口服安慰剂4剂(n=576)、ECS2a-2 4剂加生理盐水安慰剂1针(n=580)或脑膜炎球菌四价控制疫苗1针加口服安慰剂4剂(n=290)。因未发现S福氏2a感染病例，以ESBF2a-2疫苗和脑膜炎双球菌疫苗为对照组。我们将S宋内氏志贺氏菌病定义为粪便培养阳性的腹泻。对每组士兵进行2.5~7.0个月的随访。主要终点是S松内-REPA对S松内志贺氏菌病的保护作用。在4组士兵(A-D组)中发现了经培养证实的S松内志贺氏菌病病例，其中包括787名志愿者(S松内-REPA组312例，ECSF2a-2组316例，脑膜炎球菌控制疫苗159例)。A-C组志贺氏菌病病例发生在接种后70-155天，D组病例发生在接种后1-17天。在A-C组，S松内-环丙沙星治疗组志贺氏菌病的发病率为2.2%，对照组为8.6%(保护效果74%[95%可信区间28-100]，p=0.006)。D组中，S松内-环丙沙星对志贺氏菌病也有明显的保护作用(43%[4-82]，p=0.039)。免疫前和免疫后对S宋内脂多糖抗体的ELISA检测表明，患S宋内氏志贺氏菌病的接种者对同源脂多糖的血清免疫球蛋白G和IgA反应率显著低于未患同种内毒素的接种者(p=
Background The aim of this double-blind randomised vaccine-controlled trial was to assess the efficacy of a conjugate vaccine composed of Shigella sonnei O-specific polysaccharide bound to Pseudomonas aeruginosa recombinant exoprotein A (S sonnei-rEPA) and of an oral, live-attenuated Escherichia coli/S flexneri 2a (EcSf2a-2) hybrid vaccine among military recruits in Israel at high risk of exposure to Shigella spp. We report here our preliminary findings on the efficacy of S sonnei-rEPA; we have not documented sufficient cases to assess the efficacy of EcSf2a-2.Methods Between April, 1993, and August, 1994, male Israeli military recruits aged 18-22 years were asked to take part in our study. We enrolled 1446 soldiers from seven separate field sites (groups A-G). Soldiers were randomly allocated one injection of S sonnei-rEPA and four doses of oral placebo (n=576), four oral doses of EcSf2a-2 and one injection of saline placebo (n=580), or one injection of meningococcal tetravalent control vaccine and four doses of oral placebo (n=290). Because there were no cases of S flexneri 2a, the EcSf2a-2 and meningococcal vaccines were the control group. We defined S sonnei shigellosis as diarrhoea with a positive faecal culture for S sonnei. Each group of soldiers was followed up for 2.5-7.0 months. The primary endpoint was protective efficacy of S sonnei-rEPA against S sonnei shigellosis.Findings Cases of culture-proven S sonnei shigellosis occurred in four groups of soldiers (groups A-D), which comprised 787 volunteers (312 received S sonnei-rEPA, 316 received EcSf2a-2, and 159 received meningococcal control vaccine). In groups A-C, cases of shigellosis occurred 70-155 days after vaccination, whereas in group D cases occurred after 1-17 days. In groups A-C, the attack rate of shigellosis was 2.2% in recipients of S sonnei-rEPA compared with 8.6% in controls (protective efficacy 74% [95% CI 28-100], p=0.006). S sonnei-rEPA also showed significant protection against shigellosis in group D (43% [4-82], p=0.039). Prevaccination and postvaccination ELISA measurements of antibody to S sonnei lipopolysaccharide among recipients of S sonnei-rEPA showed that the vaccinees who developed S sonnei shigellosis had significantly lower serum IgG and IgA responses to the homologous lipopolysaccharide than those who did not (p=