Rahman Atiqur, Rashu Rasheduzzaman, Bhuiyan Taufiqur Rahman, Chowdhury Fahima, Khan Ashraful Islam, Islam Kamrul, LaRocque Regina C, Ryan Edward T, Wrammert Jens, Calderwood Stephen B, Qadri Firdausi, Harris Jason B
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
Clin Vaccine Immunol. 2013 Oct;20(10):1592-8. doi: 10.1128/CVI.00347-13. Epub 2013 Aug 14.
Infection with Vibrio cholerae and oral cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels of V. cholerae-specific duodenal antibodies up to 6 months after V. cholerae infection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses following V. cholerae infection using a flow cytometrically defined population and compared V. cholerae-specific responses in adult patients with V. cholerae O1 infection and vaccinees who received the OCV Dukoral (Crucell Vaccines Canada). Among flow cytometrically sorted populations of gut-homing plasmablasts, almost 50% of the cells recognized either cholera toxin B subunit (CtxB) or V. cholerae O1 lipopolysaccharide (LPS). Using a traditional enzyme-linked immunosorbent spot assay (ELISPOT), we found that infection with V. cholerae O1 and OCVs induce similar responses to the protein antigen CtxB, but responses to LPS were diminished after OCV compared to those after natural V. cholerae infection. A second dose of OCV on day 14 failed to boost circulating V. cholerae-specific plasmablast responses in Bangladeshi adults. Our results differ from those in studies from areas where cholera is not endemic, in which a second vaccination on day 14 significantly boosts plasmablast responses. Given these results, it is likely that the optimal boosting strategies for OCVs differ significantly between areas where V. cholerae infection is endemic and those where it is not.
感染霍乱弧菌和口服霍乱疫苗（OCV）会诱导短暂的循环浆母细胞反应，该反应在感染或接种疫苗后约7天达到峰值。我们之前证明，浆母细胞反应与霍乱弧菌感染后长达6个月的霍乱弧菌特异性十二指肠抗体的后续水平密切相关。因此，浆母细胞反应为粘膜表面的免疫记忆提供了一个早期窗口。在本研究中，我们使用流式细胞术定义的群体对霍乱弧菌感染后的浆母细胞反应进行了表征，并比较了成年霍乱弧菌O1感染患者和接种OCV Dukoral（加拿大Crucell疫苗公司生产）的疫苗接种者的霍乱弧菌特异性反应。在肠道归巢浆母细胞的流式细胞术分选群体中，几乎50%的细胞识别霍乱毒素B亚基（CtxB）或霍乱弧菌O1脂多糖（LPS）。使用传统的酶联免疫斑点试验（ELISPOT），我们发现霍乱弧菌O1感染和OCV诱导对蛋白质抗原CtxB的相似反应，但与自然霍乱弧菌感染后的反应相比，OCV后对LPS的反应减弱。在第14天接种第二剂OCV未能增强孟加拉国成年人循环中的霍乱弧菌特异性浆母细胞反应。我们的结果与霍乱非流行地区的研究结果不同，在这些地区，第14天进行第二次疫苗接种可显著增强浆母细胞反应。鉴于这些结果，在霍乱弧菌感染流行地区和非流行地区，OCV的最佳加强策略可能存在显著差异。
