Complete Plasmodium falciparum infection cycle model

完整的恶性疟原虫感染周期模型

• 批准号: 10592599
• 负责人: George Dimopoulos
• 金额: $ 20.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-07 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10592599
• 关键词: Achievement; Advanced Development; Anopheles Genus; Biological Assay; Biology; Blood; Communities; Culicidae; Development; Falciparum Malaria; Human; In Vitro; Infection; Laboratories; Malaria; Membrane; Methodology; Methods; Modeling; Mus; Parasites; Parasitology; Pharmaceutical Preparations; Plasmodium; Plasmodium falciparum; Publishing; Recovery; Rodent Model; Standardization; Techniques; Transgenic Organisms; asexual; drug development; feeding; humanized mouse; malaria infection; malaria transmission; mouse model; novel; pre-clinical; repository; transmission blocking; transmission process; transmission-blocking vaccine; vaccine development; vector; vector mosquito

SUMMARY A variety of novel malaria control strategies are being developed to target the parasites within the human or mosquito vector, or as they transition from vector-to-host or hos-to-vector. Most of these approaches are being studied and evaluated by using laboratory-based in vitro and rodent models in the context of malaria transmission dynamics, because to date there is no experimentally easy and affordable human Plasmodium falciparum malaria transmission model. Furthermore, the small number of in vitro-cultured P. falciparum strains capable of infecting mosquitoes represent another obstacle in the study of mosquito stages of P. falciparum infection. To maintain gametocytogenesis and mosquito infectivity, asexually grown P. falciparum cultures should either be maintained at low passage number or should be passaged through infection cycles in the mosquito vector, but these strategies also require a malaria transmission model comprising the entire human infection cycle. We have recently advanced the development of an existing humanized mouse model to enable the complete P. falciparum infection cycle, from gametocyte to gametocyte. Here we will further this achievement into a standardized, affordable and accessible human malaria infection model, thereby closing a critical gap in malaria transmission studies. In aim 1 we will explore the utility of the humanized mouse-based P. falciparum transmission model with various malaria vector species and P. falciparum isolates. In aim 2 we will investigate the utility of the humanized mouse-based P. falciparum transmission model to maintain P. falciparum gametocyte infectiousness under laboratory conditions.

概括 正在开发各种新型疟疾控制策略，以针对人类或人类内的寄生虫 蚊子向量，或它们从向量到主机或HOS向量的过渡时。这些方法中的大多数是 在疟疾传播的背景下，使用基于实验室的体外和啮齿动物模型进行了研究和评估 动力学，因为迄今为止没有实验性的简单且负担得起的人疟原虫恶性疟疾 传输模型。此外，能够感染的少量体外培养的恶性疟原虫菌株 蚊子代表了恶性疟原虫感染的蚊子阶段的另一个障碍。维护 配子细胞生成和蚊子感染性，无性地种植恶性疟原虫培养物要么维持 在低通道数或应通过蚊子载体中的感染周期传递，但是这些 策略还需要包括整个人类感染周期的疟疾传播模型。 我们最近推进了现有的人源鼠标模型的开发，以实现完整的 恶性疟原虫感染周期，从配子细胞到配子细胞。在这里，我们将这一成就进一步 标准化，负担得起且可及的人类疟疾感染模型，从而缩小了疟疾的关键差距 传输研究。在AIM 1中，我们将探索基于人源的小鼠恶性疟原虫传播的效用 具有各种疟疾载体物种和恶性疟原虫分离株的模型。在AIM 2中，我们将调查 基于人源化的小鼠恶性疟原虫传播模型，以维持恶性疟原虫的传染性。 在实验室条件下。