Development of anti-tick vaccine

抗蜱疫苗的研制

• 批准号: 12356008
• 负责人: ONUMA Misao
• 金额: $ 26.86万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12356008/
• 关键词: tick; anti-tick vaccine; recombinant antigen; Pathogens tramsmission inhibition; anti-blood feeding; serpin; ダニ抗原; ダニワクチン; カルレチクリン; 組み換え蛋白; マダニ; 節足動物媒介感染症; 組換え抗原

Maintenance of mammalian homeostatic balance is a multi-faced process involving an interaction of many proteins, however the need for a balance and coordinated interaction of many proteins, however the need for a balance and coordinated interaction between members of the serine proteinase super family and their inhibitors, known as serpins occupy a central role. In mammalian systems where extensive data exists, both serine proteinases and serpins are known to regulate such important functions as the blood coagulation cascade, fibrinolysis, food digestion, fertilization, inflammatory and immune responses. Imbalances or deficiencies in function of either serine proteinases or serpins have resulted in diseases. Ticks encode proteinases or serpins to disrupt the host homeostatic balance to their advantage.For this reason, we examined the molecular cloning of tick-encoded serpins as a candidate for tick vaccine. By using rapid amplification of the cDNA (RACE method), two genes (HLS l and HLS 2) from H. longicornis were cloned. Both recombinant HLS l and 2 showed the anti-coagulant activities. Vaccinaion of rabbits with either recombinant HLS 1 or 2 expressed in Escherichia coli resulted in significant anti-tick immunity.At present, we have characterized 4 tick salivary gland proteins whose recombinant products were effective against tick. We are planning to use these 4 cocktail vaccine for prevent the transmission of pathogens.

哺乳动物体内平衡的维持是一个多方面的过程，涉及许多蛋白质的相互作用，然而许多蛋白质之间需要平衡和协调相互作用，然而丝氨酸蛋白酶超家族成员和它们的抑制物(称为蛇毒)之间的平衡和协调相互作用起着核心作用。在存在大量数据的哺乳动物系统中，丝氨酸蛋白酶和蛇都被认为调节血液凝固级联、纤溶、食物消化、受精、炎症和免疫反应等重要功能。丝氨酸蛋白酶或蛇的功能失衡或功能缺陷都会导致疾病。壁虱编码的蛋白水解酶或蛇破坏宿主的动态平衡对它们有利。为此，我们研究了壁虱编码的蛇的分子克隆作为壁虱疫苗的候选者。利用快速扩增技术(RACE法)，克隆了长角鱼的两个基因(hls L和hls 2)。重组HLS L和2均显示出抗凝血活性。在大肠杆菌中表达的重组HLS-1或HLS-2疫苗免疫兔后，产生了显著的抗蜱免疫。目前，我们已鉴定了4种具有抗蚤活性的重组唾液腺蛋白。我们计划使用这4种鸡尾酒疫苗来预防病原体的传播。

项目成果

Mulenga A.et al.: "Characterization of an 84 kDa protein inducing an immediate hypersensitivity reaction in rabbits sensitized to Haemaphysalis longicornis ticks."Biochemica et Biophysica Acta. 1501. 219-226 (2000)

Mulenga A. 等人：“84 kDa 蛋白质的表征，该蛋白质在对长角血蜱敏感的兔子中诱导立即超敏反应。”《生物化学与生物物理学学报》。

Sugino M.: "A serine proteinase inhibitor (serpin) from ixodid tick Haemaphysalis longicornis ; cloning and preliminary assessment of its suitability as a candidate for a tick vaccine."Vaccine. (in press). (2003)

Sugino M.：“来自长角血蜱的丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂）；克隆并初步评估其作为蜱疫苗候选者的适用性。”疫苗。

Tsuda A.: "cDNA cloning, characterization and vaccine effect analysis of Haemaphysalis longicornis tick saliva proteins"Vaccine. 19. 4287-4296 (2001)

Tsuda A.：“长角血蜱唾液蛋白的cDNA克隆、表征及疫苗效果分析”疫苗。

Nakajima M.: "Passive immunization with monoclonal antibodies : effects on Haemaphysalis longicornis tick infestation of BALB/c mice"Jpn. J. Vet. Res.. (in press). (2003)

Nakajima M.：“单克隆抗体被动免疫：对 BALB/c 小鼠长角血蜱感染的影响”Jpn。

Mulenga A.: "Blood meal acquisition by tick ; Molecular advances and implication for vaccine development"Jpn. J. Vet. Res.. 49(4). 261-272 (2002)

Mulenga A.：“蜱虫获取血粉；分子进展及其对疫苗开发的影响”Jpn。