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。

• 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

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（TBV）以中断蚊子中的疟疾传播。原则上，TBV可以如下应用：（1）用于区域消除Malana； （2）保护其他疫苗或药物免受抗性寄生虫的传播。大多数领先的疟疾传播疫苗候选抗原是表面蛋白，该蛋白在疟疾寄生虫的Zygotes和kinetes上表达。这些通过使用膜喂养设备测试了测试的有效传播障碍活动。但是，从膜喂养实验获得的传输阻滞活性可能无法反映体内效率。要回答这个问题，我们需要建立动物模型系统。为了识别一个新型的TBV候选者，我们开发了识别配子细胞的单克隆抗体（MAB）。将mAb的被动转移向小鼠没有涉及任何传播阻断免疫学，这可以通过抑制MOS的卵囊发育……更多的Quito Midguts所证明。然后，为了研究针对疟原虫寄生虫的粘膜疫苗是否是诱导全身传播阻断免疫学的可行策略，将酵母合成的Pys25蛋白通过鼻腔与鼻途径与霍乱毒素（CT）联合使用，对小鼠施用。在CT存在下，PYS25的鼻内施用引起了强大的全身性体液免疫调查，这是高水平的血清IgG抗体证明的。当用PYS25/CT接种疫苗的小鼠被致死的疟原虫17x感染，然后允许按需亚噬菌体Stephensi蚊子以血餐为食时，我们发现在所有参与蚊子中，在所有参与的蚊子中都完全抑制了蚊子中虫的卵囊发育。这些结果表明，针对疟疾的粘膜疫苗是诱导有效的系统性体液传播障碍物的可行策略。因此，小鼠/啮齿动物疟疾系统是TBV研究的有用工具。较少的

项目成果

Sattabongkot J. et al.: "Blocking of transmission to mosquitoes by antibody to Plasmodium vivax malaria vaccine candidates Pvs25 And Pvs28 despite antigenic polymorphism in field isolates."American Journal of Tropical Medicine and Hygiene. 69. 536-541 (20

Sattabongkot J. 等人：“尽管野外分离株存在抗原多态性，但间日疟原虫疟疾候选疫苗 Pvs25 和 Pvs28 的抗体仍可阻断向蚊子的传播。”《美国热带医学与卫生杂志》。

Tsuboi T.et al.: "Transmission-blocking vaccine of vivax malaria."Parasitology International. 52. 1-11 (2003)

Tsuboi T.等人：“间日疟疾的传播阻断疫苗”。国际寄生虫学。

Kaneko, O., et al.: "Gene structure and expression of a Plasmodium falciparum 220-kilodalton protein homologous to the Plasmodium vivax reticulocyte binding proteins."Molecular and Biochemical Parasitlogy. 121. 275-278 (2002)

Kaneko, O. 等人：“与间日疟原虫网织红细胞结合蛋白同源的恶性疟原虫 220 千道尔顿蛋白的基因结构和表达。”分子和生化寄生虫学。

Tauboi T. et al.: "Transmission-blocking vaccine of vivax malaria."Parasitology International. 52. 1-11 (2003)

Tauboi T. 等人：“间日疟疾的传播阻断疫苗”。国际寄生虫学。

Arakawa T. et al.: "Serum antibodies induced by intranasal immunization of mice with Plasmodium vivax Pvs25 co-administered with cholera toxin completely block parasite transmission to mosquitoes."Vaccine. 21. 3143-3148 (2003)

Arakawa T.等人：“用间日疟原虫Pvs25与霍乱毒素共同给予小鼠鼻内免疫诱导的血清抗体完全阻止了寄生虫向蚊子的传播。”疫苗。