Abstract:
Cholera caused by Vibrio cholerae O139 emerged in the early 1990s and spread rapidly to 11 Asian countries before receding for unclear reasons. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). V. cholerae O139 also expresses the OSP-capsule. We, therefore, assessed antibody responses targeting V. cholerae O139 OSP, LPS, capsule, and vibriocidal responses in patients in Bangladesh with cholera caused by V. cholerae O139. We compared these responses to those of age-gender-blood group-matched recipients of the bivalent oral cholera vaccine (OCV O1/O139). We found prominent OSP, LPS, and vibriocidal responses in patients, with a high correlation between these responses. OSP responses primarily targeted the terminal tetrasaccharide of OSP. Vaccinees developed OSP, LPS, and vibriocidal antibody responses, but of significantly lower magnitude and responder frequency (RF) than matched patients. We separately analyzed responses in pediatric vaccinees born after V. cholerae O139 had receded in Bangladesh. We found that OSP responses were boosted in children who had previously received a single dose of bivalent OCV 3 yr previously but not in vaccinated immunologically naïve children. Our results suggest that OSP-specific responses occur during cholera caused by V. cholerae O139 despite the presence of capsules, that vaccination with bivalent OCV is poorly immunogenic in the short term in immunologically naïve individuals, but that OSP-specific immune responses can be primed by previous exposure, although whether such responses can protect against O139 cholera is uncertain. IMPORTANCE Cholera is a severe dehydrating illness in humans caused by Vibrio cholerae serogroups O1 or O139. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) of V. cholerae LPS. Yet, little is known about immunity to O139 OSP. In this study, we assessed immune responses targeting OSP in patients from an endemic region with cholera caused by V. cholerae O139. We compared these responses to those of the age-gender-blood group-matched recipients of the bivalent oral cholera vaccine. Our results suggest that OSP-specific responses occur during cholera caused by V. cholerae O139 and that the OSP responses primarily target the terminal tetrasaccharide of OSP. Our results further suggest that vaccination with the bivalent vaccine is poorly immunogenic in the short term for inducing O139-specific OSP responses in immunologically naïve individuals, but OSP-specific immune responses can be primed by previous exposure or vaccination.
摘要:
由霍乱弧菌O139引起的霍乱于1990年代初出现,并迅速传播到11个亚洲国家,然后因不清楚的原因而消退。对霍乱的保护是血清组特异性的,由脂多糖(LPS)的O-特异性多糖(OSP)组分定义。霍乱弧菌O139也表达OSP-胶囊。我们,因此,评估的抗体应答靶向霍乱弧菌O139OSP,LPS,胶囊,以及孟加拉国霍乱弧菌O139引起的霍乱患者的弧菌杀灭反应。我们将这些反应与二价口服霍乱疫苗(OCVO1/O139)的年龄-性别-血型匹配的接受者进行了比较。我们发现了突出的OSP,LPS,和患者的杀弧菌反应,这些反应之间有很高的相关性。OSP应答主要靶向OSP的末端四糖。接种者开发了OSP,LPS,和杀弧菌抗体反应,但幅度和应答频率(RF)明显低于匹配患者。我们分别分析了在孟加拉国O139霍乱弧菌消退后出生的儿科疫苗的反应。我们发现,OSP反应在以前3年前接受过单剂量二价OCV的儿童中得到了增强,但在免疫接种过的儿童中没有得到增强。我们的结果表明,OSP特异性反应发生在霍乱弧菌O139引起的霍乱期间,尽管存在胶囊,在免疫幼稚的个体中,用二价OCV疫苗接种在短期内免疫原性差,但是OSP特异性免疫反应可以通过先前的暴露来引发,尽管这种反应是否可以预防O139霍乱尚不确定。重要性霍乱是由O1或O139血清群霍乱弧菌引起的人类严重脱水疾病。对霍乱的保护是血清组特异性的,其由霍乱弧菌LPS的O-特异性多糖(OSP)定义。然而,对O139OSP的免疫力知之甚少。在这项研究中,我们评估了由O139霍乱弧菌引起的霍乱流行地区患者针对OSP的免疫反应.我们将这些反应与二价口服霍乱疫苗的年龄-性别-血型匹配的接受者的反应进行了比较。我们的结果表明,OSP特异性反应发生在霍乱弧菌O139引起的霍乱期间,并且OSP反应主要针对OSP的末端四糖。我们的结果进一步表明,用二价疫苗接种疫苗在短期内免疫原性差,可诱导免疫幼稚个体的O139特异性OSP反应。但是OSP特异性免疫反应可以通过先前的暴露或疫苗接种来引发。