Kuchta Alison, Rahman Taibur, Sennott Erica L, Bhuyian Taufiqur R, Uddin Taher, Rashu Rasheduzzaman, Chowdhury Fahima, Kahn Ashraf I, Arifuzzaman Mohammad, Weil Ana A, Podolsky Michael, LaRocque Regina C, Ryan Edward T, Calderwood Stephen B, Qadri Firdausi, Harris Jason B
International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh.
Clin Vaccine Immunol. 2011 Aug;18(8):1371-7. doi: 10.1128/CVI.05088-11. Epub 2011 Jun 22.
Vibrio cholerae O1 is a noninvasive enteric pathogen and serves as a model for studies of mucosal immunity. Although symptomatic V. cholerae infection induces durable protection against subsequent disease, vaccination with oral killed whole-cell V. cholerae stimulates less long-lasting protection against cholera. In this study, we demonstrated that cholera induces an early proinflammatory cellular immune response that results in priming of Th1- and Th17-type cytokine responses to ex vivo antigenic stimulation and an increase in the ratio of Th1 to Th2 CD4(+) T-cell responses. Comparable priming of Th1 and Th17 responses, with an increased ratio of Th1 to Th2 CD4(+) T-cell responses, was not observed in subjects who received two doses of the oral cholera vaccine Dukoral (a whole-cell cholera toxin B subunit containing [WC-CTB] vaccine). These findings suggest that natural V. cholerae infection induces an early, proinflammatory cellular immune response, despite the apparent lack of clinical signs of inflammation. The failure of the WC-CTB vaccine to activate equivalent, CD4(+) T-cell responses is a potential explanation for the shorter duration of protection following immunization with this vaccine. Additional studies are needed to determine whether these early T-cell-mediated events predict the subsequent duration of immunologic memory.
霍乱弧菌O1是一种非侵袭性肠道病原体,是黏膜免疫研究的模型。尽管有症状的霍乱弧菌感染可诱导对后续疾病的持久保护,但口服灭活全细胞霍乱弧菌疫苗刺激产生的针对霍乱的保护作用持续时间较短。在本研究中,我们证明霍乱可诱导早期促炎性细胞免疫反应,导致对体外抗原刺激的Th1型和Th17型细胞因子反应启动,以及Th1与Th2 CD4(+) T细胞反应比例增加。在接受两剂口服霍乱疫苗Dukoral(一种含霍乱毒素B亚单位的全细胞疫苗[WC-CTB])的受试者中,未观察到Th1和Th17反应的类似启动,以及Th1与Th2 CD4(+) T细胞反应比例增加。这些发现表明,尽管明显缺乏炎症的临床体征,但自然霍乱弧菌感染可诱导早期促炎性细胞免疫反应。WC-CTB疫苗未能激活同等的CD4(+) T细胞反应,这可能是该疫苗免疫后保护持续时间较短的一个解释。需要进一步研究以确定这些早期T细胞介导的事件是否能预测后续免疫记忆的持续时间。