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.

总结 正在开发各种新的疟疾控制策略，以针对人体内的寄生虫， 蚊子媒介，或当它们从媒介到宿主或宿主到媒介的转变。这些方法中的大多数都是 在疟疾传播的背景下，使用实验室体外模型和啮齿动物模型进行研究和评价 动态，因为迄今为止，没有实验上容易和负担得起的人类恶性疟原虫疟疾 传输模型此外，少量体外培养的恶性疟原虫菌株能够感染 蚊子是研究恶性疟原虫感染的蚊子阶段的另一个障碍。保持 配子体发生和蚊子感染性，无性生长的恶性疟原虫培养物应保持 或应通过蚊子媒介中的感染循环进行传代，但这些 这些战略还需要一个包括整个人类感染周期的疟疾传播模型。 我们最近已经推进了现有人源化小鼠模型的开发，以使完整的 P.恶性疟原虫感染周期，从配子体到配子体。在这里，我们将进一步将这一成就转化为一个 标准化、负担得起和可获得的人类疟疾感染模型，从而缩小疟疾防治方面的重大差距 传输研究。在目标1中，我们将探索基于小鼠的人源化恶性疟原虫传播的实用性 用各种疟疾病媒物种和恶性疟原虫分离株建立模型。在aim 2中，我们将研究 维持恶性疟原虫配子体感染性的基于小鼠的人源化恶性疟原虫传播模型 在实验室条件下。