Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Distrito Federal, México.
PLoS One. 2010 Jun 23;5(6):e11287. doi: 10.1371/journal.pone.0011287.
Cysticercosis and hydatidosis seriously affect human health and are responsible for considerable economic loss in animal husbandry in non-developed and developed countries. S3Pvac and EG95 are the only field trial-tested vaccine candidates against cysticercosis and hydatidosis, respectively. S3Pvac is composed of three peptides (KETc1, GK1 and KETc12), originally identified in a Taenia crassiceps cDNA library. S3Pvac synthetically and recombinantly expressed is effective against experimentally and naturally acquired cysticercosis.
METHODOLOGY/PRINCIPAL FINDINGS: In this study, the homologous sequences of two of the S3Pvac peptides, GK1 and KETc1, were identified and further characterized in Taenia crassiceps WFU, Taenia solium, Taenia saginata, Echinococcus granulosus and Echinococcus multilocularis. Comparisons of the nucleotide and amino acid sequences coding for KETc1 and GK1 revealed significant homologies in these species. The predicted secondary structure of GK1 is almost identical between the species, while some differences were observed in the C terminal region of KETc1 according to 3D modeling. A KETc1 variant with a deletion of three C-terminal amino acids protected to the same extent against experimental murine cysticercosis as the entire peptide. On the contrary, immunization with the truncated GK1 failed to induce protection. Immunolocalization studies revealed the non stage-specificity of the two S3Pvac epitopes and their persistence in the larval tegument of all species and in Taenia adult tapeworms.
CONCLUSIONS/SIGNIFICANCE: These results indicate that GK1 and KETc1 may be considered candidates to be included in the formulation of a multivalent and multistage vaccine against these cestodiases because of their enhancing effects on other available vaccine candidates.
囊尾蚴病和包虫病严重影响人类健康,在欠发达国家和发达国家的畜牧业中造成了相当大的经济损失。S3Pvac 和 EG95 分别是针对囊尾蚴病和包虫病的唯一经过现场试验测试的候选疫苗。S3Pvac 由三个肽(KETc1、GK1 和 KETc12)组成,最初在猪带绦虫 cDNA 文库中被鉴定出来。S3Pvac 经合成和重组表达后,对实验性和自然获得性囊尾蚴病均有效。
方法/主要发现:在这项研究中,鉴定并进一步分析了 S3Pvac 中两个肽 GK1 和 KETc1 的同源序列,这些肽在阔节裂头绦虫 WFU、猪带绦虫、牛带绦虫、细粒棘球绦虫和多房棘球绦虫中均有发现。对编码 KETc1 和 GK1 的核苷酸和氨基酸序列的比较显示,这些物种之间存在显著的同源性。GK1 的预测二级结构在这些物种之间几乎相同,而根据 3D 建模,在 KETc1 的 C 末端区域观察到一些差异。与全长肽一样,缺失三个 C 末端氨基酸的 KETc1 变体对实验性小鼠囊尾蚴病具有相同程度的保护作用。相反,用截短的 GK1 免疫未能诱导保护。免疫定位研究表明,这两个 S3Pvac 表位具有非阶段性特异性,并且在所有物种的幼虫外被和绦虫成虫中都能持续存在。
结论/意义:这些结果表明,由于 GK1 和 KETc1 对其他现有候选疫苗具有增强作用,因此它们可能被视为包含在针对这些囊尾蚴病的多价多阶段疫苗中的候选物。