Johnson Russell A, Uddin Taher, Aktar Amena, Mohasin M, Alam Mohammad Murshid, Chowdhury Fahima, Harris Jason B, LaRocque Regina C, Bufano Meagan Kelly, Yu Yanan, Wu-Freeman Ying, Leung Daniel T, Sarracino David, Krastins Bryan, Charles Richelle C, Xu Peng, Kovác Pavol, Calderwood Stephen B, Qadri Firdausi, Ryan Edward T
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
Clin Vaccine Immunol. 2012 Nov;19(11):1712-21. doi: 10.1128/CVI.00321-12. Epub 2012 Sep 19.
Immunity against Vibrio cholerae O1 is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) part of lipopolysaccharide (LPS). Despite this, human immune responses to V. cholerae OSP have not previously been characterized. We assessed immune responses against V. cholerae OSP in adults with cholera caused by V. cholerae O1 El Tor serotype Inaba or Ogawa in Dhaka, Bangladesh, using O1 OSP-core-bovine serum albumin (OSPc:BSA) conjugates; responses targeted OSP in these conjugates. Responses of Inaba-infected patients to Inaba OSP and LPS increased significantly in IgG, IgM, and IgA isotypes from the acute to convalescent phases of illness, and the responses correlated well between OSP and LPS (R = 0.86, 0.73, and 0.91, respectively; P < 0.01). Plasma IgG, IgM, and IgA responses to Ogawa OSP and LPS in Ogawa-infected patients also correlated well with each other (R = 0.60, 0.60, and 0.92, respectively; P < 0.01). Plasma IgM responses to Inaba OSP and Ogawa OSP correlated with the respective serogroup-specific vibriocidal antibodies (R = 0.80 and 0.66, respectively; P < 0.001). Addition of either OSPc:BSA or LPS, but not BSA, to vibriocidal assays inhibited vibriocidal responses in a comparable and concentration-dependent manner. Mucosal IgA immune responses to OSP and LPS were also similar. Our study is the first to characterize anti-OSP immune responses in patients with cholera and suggests that responses targeting V. cholerae LPS, including vibriocidal responses that correlate with protection against cholera, predominantly target OSP. Induction of anti-OSP responses may be associated with protection against cholera, and our results may support the development of a vaccine targeting V. cholerae OSP.
针对霍乱弧菌O1的免疫具有血清群特异性，血清群分类由脂多糖（LPS）的O特异性多糖（OSP）部分决定。尽管如此，此前人类对霍乱弧菌OSP的免疫反应尚未得到表征。我们在孟加拉国达卡对由霍乱弧菌O1埃尔托血清型稻叶或小川引起霍乱的成人中，使用O1 OSP-核心-牛血清白蛋白（OSPc:BSA）偶联物评估了针对霍乱弧菌OSP的免疫反应；反应针对这些偶联物中的OSP。稻叶感染患者对稻叶OSP和LPS的反应在疾病急性期到恢复期的IgG、IgM和IgA同种型中显著增加，并且OSP和LPS之间的反应相关性良好（分别为R = 0.86、0.73和0.91；P < 0.01）。小川感染患者血浆中对小川OSP和LPS的IgG、IgM和IgA反应彼此之间也相关性良好（分别为R = 0.60、0.60和0.92；P < 0.01）。血浆中对稻叶OSP和小川OSP的IgM反应与各自血清群特异性的杀弧菌抗体相关（分别为R = 0.80和0.66；P < 0.001）。在杀弧菌试验中添加OSPc:BSA或LPS，但不添加BSA，以类似且浓度依赖的方式抑制杀弧菌反应。对OSP和LPS的黏膜IgA免疫反应也相似。我们的研究首次表征了霍乱患者的抗OSP免疫反应，并表明针对霍乱弧菌LPS的反应，包括与预防霍乱相关的杀弧菌反应，主要针对OSP。抗OSP反应的诱导可能与预防霍乱有关，我们的结果可能支持开发针对霍乱弧菌OSP的疫苗。
