Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
PLoS Negl Trop Dis. 2019 Nov 19;13(11):e0007874. doi: 10.1371/journal.pntd.0007874. eCollection 2019 Nov.
Antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae may protect against cholera; however, little is known about this immune response in infected immunologically naïve humans.
We measured serum anti-OSP antibodies in adult North American volunteers experimentally infected with V. cholerae O1 Inaba El Tor N16961. We also measured vibriocidal and anti-cholera toxin B subunit (CtxB) antibodies and compared responses to those in matched cholera patients in Dhaka, Bangladesh, an area endemic for cholera.
We found prominent anti-OSP antibody responses following initial cholera infection: these responses were largely IgM and IgA, and highest to infecting serotype with significant cross-serotype reactivity. The anti-OSP responses peaked 10 days after infection and remained elevated over baseline for ≥ 6 months, correlated with vibriocidal responses, and may have been blunted in blood group O individuals (IgA anti-OSP). We found significant differences in immune responses between naïve and endemic zone cohorts, presumably reflecting previous exposure in the latter.
Our results define immune responses to O-specific polysaccharide in immunologically naive humans with cholera, find that they are largely IgM and IgA, may be blunted in blood group O individuals, and differ in a number of significant ways from responses in previously humans. These differences may explain in part varying degrees of protective efficacy afforded by cholera vaccination between these two populations.
ClinicalTrials.gov NCT01895855.
针对霍乱弧菌 O 特异性多糖 (OSP) 的抗体可能具有预防霍乱的作用;然而,对于感染后免疫功能尚未成熟的人群中的这种免疫反应,人们知之甚少。
我们测量了北美成年志愿者在实验性感染霍乱弧菌 O1 型 Inaba El Tor N16961 后的血清抗 OSP 抗体。我们还测量了杀菌和抗霍乱毒素 B 亚单位 (CtxB) 抗体,并将这些反应与孟加拉国达卡地区匹配的霍乱患者的反应进行了比较,该地区是霍乱的流行区。
我们在初次感染后发现了明显的抗 OSP 抗体反应:这些反应主要是 IgM 和 IgA,对感染血清型的反应最高,并有显著的交叉血清型反应。抗 OSP 反应在感染后 10 天达到峰值,并在基线以上持续升高至少 6 个月,与杀菌反应相关,并且在血型为 O 的个体中可能减弱(IgA 抗 OSP)。我们发现了在感染后免疫功能尚未成熟的人群和流行地区人群之间的免疫反应存在显著差异,这可能反映了后者的先前暴露。
我们的结果定义了免疫功能尚未成熟的人群中针对霍乱弧菌 O 特异性多糖的免疫反应,发现这些反应主要是 IgM 和 IgA,在血型为 O 的个体中可能减弱,并且在许多方面与先前人群的反应存在显著差异。这些差异可能在一定程度上解释了两种人群中霍乱疫苗提供的保护效力程度不同。
ClinicalTrials.gov NCT01895855。