International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) , Dhaka, Bangladesh.
Division of Infectious Diseases, Massachusetts General Hospital , Boston, Massachusetts, USA.
mSphere. 2023 Oct 24;8(5):e0025523. doi: 10.1128/msphere.00255-23. Epub 2023 Aug 30.
Cholera caused by 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). O139 also expresses the OSP-capsule. We, therefore, assessed antibody responses targeting O139 OSP, LPS, capsule, and vibriocidal responses in patients in Bangladesh with cholera caused by 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 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 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 serogroups O1 or O139. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) of 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 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 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.
霍乱弧菌 O139 于 20 世纪 90 年代初出现，并迅速传播到 11 个亚洲国家，之后原因不明地消退。对霍乱的保护是血清型特异性的，这是由脂多糖 (LPS) 的 O 特异性多糖 (OSP) 成分定义的。O139 还表达 OSP 荚膜。因此，我们评估了孟加拉国 O139 霍乱患者针对 O139 OSP、LPS、荚膜和杀菌反应的抗体反应。我们将这些反应与年龄、性别、血型匹配的双价口服霍乱疫苗 (OCV O1/O139) 接受者的反应进行了比较。我们发现患者中存在明显的 OSP、LPS 和杀菌反应，这些反应之间具有高度相关性。OSP 反应主要针对 OSP 的末端四糖。疫苗接种者产生 OSP、LPS 和杀菌抗体反应，但反应幅度和反应频率 (RF) 明显低于匹配的患者。我们分别分析了孟加拉国 O139 消退后出生的儿科疫苗接种者的反应。我们发现，以前接受过双价 OCV 单剂量接种的 3 岁儿童的 OSP 反应得到了增强，但未接受过免疫的免疫原性儿童的 OSP 反应没有增强。我们的结果表明，尽管存在荚膜，O139 霍乱弧菌仍会引起 OSP 特异性反应，双价 OCV 在短期内对免疫原性个体的免疫原性较差，但 OSP 特异性免疫反应可通过先前暴露而引发，尽管这种反应是否能预防 O139 霍乱尚不确定。重要性 霍乱是人类由 O 组血清群 O1 或 O139 引起的一种严重的脱水性疾病。对霍乱的保护是血清型特异性的，这是由 LPS 的 O 特异性多糖 (OSP) 定义的。然而，人们对 O139 OSP 的免疫了解甚少。在这项研究中，我们评估了流行地区 O139 霍乱患者针对 OSP 的免疫反应。我们将这些反应与年龄、性别、血型匹配的双价口服霍乱疫苗接受者的反应进行了比较。我们的研究结果表明，O139 霍乱弧菌会引起 OSP 特异性反应，并且 OSP 反应主要针对 OSP 的末端四糖。我们的研究结果进一步表明，双价疫苗在短期内对诱导免疫原性个体的 O139 特异性 OSP 反应的免疫原性较差，但 OSP 特异性免疫反应可通过先前暴露或接种来引发。
