Caenorhabditis elegans as an expression system for vaccine candidates of parasitic nematodes

秀丽隐杆线虫作为寄生线虫候选疫苗的表达系统

• 批准号: BB/F002033/1
• 负责人: Collette Britton
• 金额: $ 36.95万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF002033%2F1
• 关键词: Caenorhabditis; elegans; expression; system; vaccine

Parasitic nematode (worm) infections of humans and livestock cause major health, welfare and economic problems worldwide. The efficiency of drugs currently available to control parasitic nematode infections is decreasing due to the emergence of drug-resistant parasites and alternative control approaches are urgently needed. Validation of new drug or vaccine targets of parasitic nematodes is hampered by the difficulty of obtaining sufficient parasite material for testing. Parasite proteins produced artificially in bacteria, yeast or insect cells are often folded incorrectly and/or fail to be modified in the same way as the normal parasite protein. This affects the proteins' ability to stimulate protective immune responses to infection, required for an effective vaccine, and their ability to interact with inhibitors, required for drug design. Development of a system which can synthesise protein in a similar form to the protein present within the worm would, therefore, be advantageous to parasite vaccine and drug research. Parasitic nematodes are closely related to the free-living nematode Caenorhabditis elegans and many of the proteins made in free-living and parasitic nematodes are similar. We have successfully used C. elegans to synthesise a parasite enzyme and shown that the enzyme is active, can interact with inhibitors and is modified correctly. Sufficient protein was expressed for vaccine studies to be carried out. We now propose to use the C. elegans system to make a previously identified, highly effective vaccine candidate of a major sheep parasitic nematode. We will compare the folding and modifications of the C. elegans synthesised protein to the normal parasite protein and test its ability to protect sheep against nematode disease. This work can be developed to generate other important parasite proteins and will be important both to basic research of nematode proteins and to commercial vaccine development. We will link with other researchers with expertise in animal parasite control and with industry (Pfizer) to achieve our aims.

人类和牲畜的寄生线虫感染（蠕虫）在全球范围内引起重大健康，福利和经济问题。由于抗药性寄生虫的出现，目前可用于控制寄生线虫感染的药物效率正在降低，并且迫切需要替代控制方法。难以获得足够的寄生虫材料进行测试的验证寄生虫线虫的新药或疫苗靶标受到阻碍。在细菌，酵母菌或昆虫细胞中人为产生的寄生虫蛋白通常会错误地折叠和/或无法以与正常寄生虫蛋白相同的方式修饰。这会影响蛋白质刺激有效疫苗所需的保护性免疫反应的能力，以及它们与抑制剂相互作用所需的能力。因此，可以开发可以以类似于蠕虫中存在的蛋白质形式合成蛋白质的系统，因此对寄生虫疫苗和药物研究有利。寄生线虫与秀丽隐杆线虫的自由线虫密切相关，并且在自由生活和寄生线虫中制造的许多蛋白质相似。我们已经成功使用了秀丽隐杆线虫来合成寄生虫酶，并表明该酶是活性的，可以与抑制剂相互作用并正确修饰。表达足够的蛋白质以进行疫苗研究。现在，我们建议使用秀丽隐杆线虫系统制作主要的绵羊寄生虫的先前高效的疫苗候选者。我们将比较秀丽隐杆线虫合成蛋白与正常寄生虫蛋白的折叠和修饰，并测试其保护绵羊免受线虫疾病的能力。可以开发这项工作来产生其他重要的寄生虫蛋白，对于线虫蛋白的基础研究和商业疫苗开发都至关重要。我们将与其他具有动物寄生虫控制和行业（辉瑞）专业知识的研究人员联系，以实现我们的目标。

项目成果

Melanisation of Teladorsagia circumcincta larvae exposed to sunlight: a role for GTP-cyclohydrolase in nematode survival.

Teladorsagiacircumcincta 幼虫暴露在阳光下的黑化：GTP-环水解酶在线虫存活中的作用。

• DOI: 10.1016/j.ijpara.2012.06.005
• 发表时间: 2012
• 期刊: International journal for parasitology
• 影响因子: 4
• 作者: Baker RH

Parasitic Helminths - Targets, Screens, Drugs and Vaccines

寄生蠕虫 - 目标、筛查、药物和疫苗

• DOI: 10.1002/9783527652969.ch6
• 发表时间: 2012
• 作者: Britton C

Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans.

• DOI: 10.1186/1297-9716-44-111
• 发表时间: 2013-12-01
• 期刊: Veterinary research
• 影响因子: 4.4
• 作者: Roberts B;Antonopoulos A;Haslam SM;Dicker AJ;McNeilly TN;Johnston SL;Dell A;Knox DP;Britton C
• 通讯作者: Britton C