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

目前正在研制阻断传播疫苗，以阻断疟疾通过蚊子传播。原则上，TBV可用于以下用途：（1）用于区域性疟疾的消灭;（2）保护其他疫苗或药物，防止耐药寄生虫的传播。大多数主要的疟疾传播阻断疫苗候选抗原是在疟原虫的受精卵和动合子上表达的表面蛋白。这些引发有效的传输阻断活性测试使用膜饲养装置。然而，从膜喂养实验中获得的传递阻断活性可能不反映体内功效。要回答这个问题，需要建立动物模型体系。为了鉴定一种新的TBV候选物，我们开发了一组识别配子母细胞的单克隆抗体（mAb）。通过对小鼠卵囊发育的抑制证明，将mAb被动转移给小鼠并没有赋予任何传播阻断免疫力。 ...更多信息 你的内脏。然后，为了研究针对疟原虫动合子表面蛋白的粘膜疫苗是否是诱导全身性传播阻断免疫的可行策略，将酵母合成的Pys 25蛋白与霍乱毒素（CT）（一种有效的粘膜佐剂）组合通过鼻途径给予小鼠。在CT存在下鼻内施用Pys 25诱导强的全身体液免疫应答，如高水平的血清IgG抗体所证明的。当接种Pys 25/CT的小鼠感染致死株约氏疟原虫17 X，然后让斯氏按蚊以它们的血餐为食时，我们发现在所有检查的充血蚊子中，蚊子中肠中的卵囊发育完全受到抑制。这些结果表明，针对疟疾动合子表面蛋白的粘膜疫苗是诱导有效的系统性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研究的有用工具。少

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