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Development of animal model for novel transmission-blocking vaccine research using gamete surface proteins of Plasmodium yoelii.

使用约氏疟原虫配子表面蛋白开发用于新型传播阻断疫苗研究的动物模型。

基本信息

批准号：
14570215
负责人：
TSUBOI Takafumi
金额：
$ 2.24万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570215/
关键词：
Malaria transmission-blocking vaccine gamete animal model monoclonal antibody マラリア

项目摘要

Transmission-blocking vaccines (TBV) are being developed to interrupt malaria transmission in the mosquito vector. In principle, TBVs can be applied as follows : (1)for regional elimination of malana ; and (2) protection of other vaccines or drugs against the spread of resistant parasites. Most leading malaria transmission-blocking vaccine candidate antigens are surface proteins expressed on zygotes and ookinetes of the malaria parasites. These elicit potent transmission-blocking activity tested by using membrane-feeding apparatus. However, the transmission-blocking activity obtained from the membrane-feeding experiment may not reflect the in vivo efficacy. To answer this question, we need to establish animal model system. To identify a novel TBV candidate, we have developed a panel of monoclonal antibodies (mAb), which recognize gametocytes. Passive transfer of the mAb to mice did not confer any transmission-blocking immunity as evidenced by the inhibition of oocyst development in mos … More quito midguts. Then, to investigate whether mucosal vaccines against malaria parasite ookinete surface proteins are a viable strategy for the induction of systemic transmission-blocking immunity, the yeast-synthesized Pys25 protein was administered to mice via nasal routes in combination with cholera toxin (CT), a potent mucosal adjuvant. Intranasal administrations of Pys25 in the presence of CT induced strong systemic humoral immune responses as evidenced by high levels of serum IgG antibodies. When mice vaccinated with Pys25/CT were infected with a lethal strain of Plasmodium yoelii 17X, followed by allowing Anopheles stephensi mosquitoes to feed on their blood meals, we found that oocyst development in mosquito midguts was completely inhibited in all engorged mosquitoes examined. These results suggest that mucosal vaccines against malaria ookinete surface proteins are a feasible strategy for the induction of effective systemic humoral transmission-blocking immunity; therefore, mouse/rodent malaria system is a useful tool for the TBV study. Less

正在开发传播阻断疫苗，以阻断疟疾在蚊子媒介中的传播。原则上，TBVs可以应用于以下方面：(1)区域消除malana；(2)保护其他疫苗或药物免受耐药寄生虫的传播。大多数主要的疟疾传播阻断疫苗候选抗原是在疟疾寄生虫的受精卵和卵母细胞上表达的表面蛋白。这些诱发了有效的传输阻断活性，通过膜摄食装置进行了测试。然而，从膜喂养实验中获得的传输阻断活性可能不能反映体内功效。为了回答这个问题，我们需要建立动物模型系统。为了鉴定一种新的TBV候选者，我们开发了一组单克隆抗体（mAb），可以识别配子细胞。单抗被动转移到小鼠身上没有产生任何传输阻断免疫，这可以通过抑制大多数小鼠的卵囊发育来证明。然后，为了研究针对疟疾寄生虫卵胞体表面蛋白的粘膜疫苗是否是诱导系统性传播阻断免疫的可行策略，我们将酵母合成的Pys25蛋白与霍乱毒素（一种有效的粘膜佐剂）联合通过鼻腔给药给小鼠。经鼻给药的Pys25存在CT诱导强烈的全身体液免疫反应，证明了高水平的血清IgG抗体。当接种Pys25/CT的小鼠感染致死的约氏疟原虫17X菌株，然后让斯氏按蚊以其血餐为食时，我们发现在所有被检查的充血的蚊子中，卵囊的发育完全被抑制。这些结果表明，针对疟疾卵胞体表面蛋白的粘膜疫苗是诱导有效的全身体液传播阻断免疫的可行策略；因此，小鼠/啮齿动物疟疾系统是TBV研究的一个有用工具。少