Haemoglobin degrading proteases as targets of anti-hookworm vaccines

血红蛋白降解蛋白酶作为抗钩虫疫苗的靶标

• 批准号: nhmrc : 389813
• 负责人: Prof Alexander Loukas
• 金额: $ 34.86万
• 依托单位: Queensland Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/haemoglobin-degrading-proteases-hookworm-vaccines/99717
• 关键词: Haemoglobin; degrading; proteases; targets; anti

Blood-feeding worms ingest red blood cells and disrupt them in the intestine, releasing haemogobin (Hb). We have recently shown that canine hookworms employ a battery of distinct proteolytic enzymes, termed haemoglobinases, which digest Hb. The families of proteases used and the order in which they act are strikingly similar to the defined catalytic pathway used by the malaria parasite to digest Hb in its food vacuole. Recent work from our laboratory has shown that these proteases are effective as vaccines against canine hookworm disease by interfering with the worm's ability to feed on blood and obtain suitable nutrition. This in turn affects the ability of female worms to lay eggs, thereby potentially disrupting transmission of the parasites. We now propose to identify the genes encoding haemoglobinases from the human hookworm, Necator americanus, determine the ordered pathway of Hb degradation and explore in vitro correlates of the effectiveness of a haemoglobinase vaccine in animal models of hookworm infection and pathogenesis.

吸血蠕虫摄取红细胞并在肠道中破坏它们，释放血红蛋白（Hb）。我们最近发现，犬钩虫采用一组不同的蛋白水解酶，称为血红蛋白酶，消化血红蛋白。使用的蛋白酶家族和它们的作用顺序与疟原虫在其食物泡中消化Hb所使用的确定的催化途径惊人地相似。我们实验室最近的工作表明，这些蛋白酶通过干扰蠕虫以血液为食和获得适当营养的能力，作为预防犬钩虫病的疫苗是有效的。这反过来又会影响雌性蠕虫产卵的能力，从而可能破坏寄生虫的传播。我们现在提出，以确定编码血红蛋白酶的基因，从人类钩虫，美洲钩虫，确定有序的途径，血红蛋白降解和探讨在体外相关的血红蛋白酶疫苗的有效性，钩虫感染和发病机制的动物模型。