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首页> 外文期刊>Human vaccines >Lipid core peptide targeting the cathepsin D hemoglobinase of Schistosoma mansoni as a component of a schistosomiasis vaccine
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Lipid core peptide targeting the cathepsin D hemoglobinase of Schistosoma mansoni as a component of a schistosomiasis vaccine

机译：血吸虫病疫苗中靶向曼氏血吸虫组织蛋白酶D血红蛋白酶的脂质核心肽

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摘要

The self-adjuvanting lipid core peptide (LCP) system offers a safe alternative vaccine delivery strategy, eliminating the need for additional adjuvants such as CpG Alum. In this study, we adopted the LCP as a scaffold for an epitope located on the surface of the cathepsin D hemoglobinase (Sm-CatD) of the human blood fluke Schistosoma mansoni. Sm-CatD plays a pivotal role in digestion of the fluke's bloodmeal and has been shown to be efficacious as a subunit vaccine in a murine model of human schistosomiasis. Using molecular modeling we showed that S. mansoni cathepsin D possesses a predicted surface exposed alpha-helix (A_(263)K) that corresponds to an immunodominant helix and target of enzyme-neutralizing antibodies against Necator americanus APR-1 (Na-APR-1), the orthologous protease and vaccine antigen from blood-feeding hookworms. The A_(263)K epitope was engineered as two peptide variants, one of which was flanked at both termini with a coil maintaining sequence, thereby promoting the helical characteristics of the native A_(263)K epitope. Some of the peptides were fused to a self-adjuvanting lipid core scaffold to generate LCPs. Mice were vaccinated with unadjuvanted peptides, peptides formulated with Freund's adjuvants, or LCPs. Antibodies generated to LCPs recognized native Sm-CatD within a soluble adult schistosome extract, and almost completely abolished its enzymatic activity in vitro. Using immunohistochemistry we showed that anti-LCP antibodies bound to the native Sm-CatD protein in the esophagus and anterior regions of the gastrodermis of adult flukes. Vaccines offer an alternative control strategy in the fight against schistosomiasis, and further development of LCPs containing multiple epitopes from this and other vaccine antigens should become a research priority.
机译：自佐剂脂质核心肽（LCP）系统提供了一种安全的替代疫苗递送策略，从而消除了对其他佐剂（例如CpG明矾）的需求。在这项研究中，我们采用LCP作为人类血吸虫曼氏血吸虫组织蛋白酶D血红蛋白酶（Sm-CatD）表面表位的支架。 Sm-CatD在吸虫吸食过程中起着举足轻重的作用，在人类血吸虫病小鼠模型中已显示出作为亚单位疫苗的功效。使用分子模型，我们显示曼氏链球菌组织蛋白酶D具有预测的表面暴露的α-螺旋（A_（263）K），该螺旋对应于免疫优势螺旋和针对美国黑猫APR-1（Na-APR- 1），取血钩虫的直系同源蛋白酶和疫苗抗原。 A_（263）K表位被工程化为两个肽变体，其中一个在两个末端均侧翼具有线圈保持序列，从而促进了天然A_（263）K表位的螺旋特征。一些肽与自佐剂脂质核心支架融合以产生LCP。给小鼠接种未佐剂的肽，用弗氏佐剂配制的肽或LCP。针对LCP产生的抗体识别可溶性成人血吸虫提取物中的天然Sm-CatD，并在体外几乎完全消除了其酶促活性。使用免疫组织化学，我们显示了抗LCP抗体与成年吸虫的食道和胃真皮前区中的天然Sm-CatD蛋白结合。在对抗血吸虫病方面，疫苗提供了另一种控制策略，进一步开发包含来自该抗原和其他疫苗抗原的多个表位的LCP成为研究重点。

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