Zhang T, Li E, Stanley S L
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Infect Immun. 1995 Apr;63(4):1349-55. doi: 10.1128/iai.63.4.1349-1355.1995.
The intestinal protozoan parasite Entamoeba histolytica causes amebic dysentery, a major cause of morbidity worldwide. The induction of a mucosal antibody response capable of blocking amebic adhesion to intestinal cells could represent an approach to preventing E. histolytica infection and disease. Here we describe the expression of a chimeric protein containing an immunogenic dodecapeptide derived from the serine-rich E. histolytica protein (SREHP), fused to the cholera toxin B subunit (CtxB). The CtxB-SREHP-12 chimeric protein was purified from Escherichia coli lysates and retained the critical GM1 ganglioside-binding activity of the CtxB moiety. Mice fed the CtxB-SREHP-12 fusion protein along with a subclinical dose of cholera toxin developed mucosal immunoglobulin A and immunoglobulin G and systemic antibody responses that recognized recombinant and native SREHP. Our study confirms the feasibility of inducing mucosal immune responses to immunogenic peptides by their genetic fusion to the CtxB subunit and identifies the CtxB-SREHP-12 chimeric protein as a candidate oral vaccine to prevent E. histolytica infection.
肠道原生动物寄生虫溶组织内阿米巴可引起阿米巴痢疾,这是全球发病的主要原因之一。诱导能够阻断阿米巴对肠道细胞粘附的粘膜抗体反应可能是预防溶组织内阿米巴感染和疾病的一种方法。在此,我们描述了一种嵌合蛋白的表达,该蛋白包含源自富含丝氨酸的溶组织内阿米巴蛋白(SREHP)的免疫原性十二肽,并与霍乱毒素B亚基(CtxB)融合。CtxB-SREHP-12嵌合蛋白从大肠杆菌裂解物中纯化得到,并保留了CtxB部分关键的GM1神经节苷脂结合活性。用CtxB-SREHP-12融合蛋白与亚临床剂量的霍乱毒素一起喂养的小鼠产生了粘膜免疫球蛋白A和免疫球蛋白G以及识别重组和天然SREHP的全身抗体反应。我们的研究证实了通过将免疫原性肽与CtxB亚基进行基因融合来诱导粘膜免疫反应的可行性,并确定CtxB-SREHP-12嵌合蛋白作为预防溶组织内阿米巴感染的候选口服疫苗。