Soong C J, Torian B E, Abd-Alla M D, Jackson T F, Gatharim V, Ravdin J I
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Infect Immun. 1995 Feb;63(2):472-7. doi: 10.1128/iai.63.2.472-477.1995.
The goal of our study was to obtain a highly conserved Entamoeba histolytica recombinant antigen for study as a subunit amebiasis vaccine. We screened a Uni-Zap cDNA library of E. histolytica (strain HM1:IMSS) with human immune sera and isolated a dominant 804-bp cDNA clone. A 33-kDa fusion protein expressed from the cDNA clone was determined by monoclonal antibody binding, DNA hybridization, and nucleotide sequence to be the complete E. histolytica 29-kDa antigen. Serum antibodies to the recombinant protein were detected by enzyme-linked immunosorbent assay in 80% of subjects from Egypt and South Africa with amebic liver abscess. Similar results were found with the native 29-kDa protein. Native and recombinant 29-kDa antigens induced proliferation of lymphocytes harvested from patients with amebic liver abscess (P < 0.01 compared with controls). Intraperitoneal immunization of gerbils with the recombinant fusion protein (10 micrograms) with Titermax adjuvant elicited an antigen-specific serum immunoglobulin G antibody response and was partially protective (54%) against intrahepatic challenge with 5 x 10(5) virulent axenic trophozoites (strain HM1:IMSS). In summary, the recombinant form of the E. histolytica 29-kDa antigen demonstrated serologic specificity for amebic liver abscess, exhibited conserved T-cell epitopes, and was effective as a subunit vaccine in an experimental animal model of amebic liver abscess.
我们研究的目的是获得一种高度保守的溶组织内阿米巴重组抗原,用于作为亚单位阿米巴病疫苗进行研究。我们用人免疫血清筛选了溶组织内阿米巴(菌株HM1:IMSS)的Uni-Zap cDNA文库,分离出一个占主导地位的804 bp cDNA克隆。通过单克隆抗体结合、DNA杂交和核苷酸序列测定,从该cDNA克隆表达的一种33 kDa融合蛋白为完整的溶组织内阿米巴29 kDa抗原。通过酶联免疫吸附测定法在80%的患有阿米巴肝脓肿的埃及和南非受试者中检测到了针对该重组蛋白的血清抗体。天然29 kDa蛋白也得到了类似结果。天然和重组29 kDa抗原均可诱导从阿米巴肝脓肿患者采集的淋巴细胞增殖(与对照组相比,P < 0.01)。用重组融合蛋白(10微克)与Titermax佐剂对沙鼠进行腹腔免疫,可引发抗原特异性血清免疫球蛋白G抗体反应,并对5×10⁵ 有毒无菌滋养体(菌株HM1:IMSS)的肝内攻击具有部分保护作用(54%)。总之,溶组织内阿米巴29 kDa抗原的重组形式对阿米巴肝脓肿具有血清学特异性,表现出保守的T细胞表位,并且在阿米巴肝脓肿的实验动物模型中作为亚单位疫苗是有效的。