SBIR Phase I: Novel Urine-excreted Plasmodium Falciparum and P. vivax Poly-asparagine Proteins as Targets for Bi-specific Monoclonal Antibody and Urine Malaria Test Development

该小型企业创新研究I期项目旨在利用发热性疟疾患者尿液中脱落的新型恶性疟原虫（Pf）和间日疟原虫（Pv）蛋白质开发一种双价单克隆抗体。使用生物信息学的方法，我们将创建，评分，并选择在硅片上生成的天然抗原变体的重组体，旨在表达马赛克，最大限度地在一个结构中包含共同的潜力，并尽量减少罕见的表位。重组抗原的抗原特性通过间接ELISA使用来自表面健康个体和临床Pf和Pv疟疾患者的充分表征的血清组来验证。使用来自Pf/Pv流行地区的一系列临床尿液样品在试纸测试中评估重组抗体的效用。我们的总体目标是开发一种简单的一步尿基试纸测试的同时，但具体的诊断临床Pf和/或Pv疟疾。该项目更广泛的影响/商业潜力涉及开发一种基础广泛的一步尿检，用于发热患者的临床Pf和/或Pv疟疾的家庭或护理点诊断。该测试可能提供一种可靠的工具来区分有症状和无症状的疾病，并为有需要的人提供更好的治疗选择。这将有可能使疟疾流行地区，特别是偏远地区和经常发生混合感染的地方，更广泛地接受疟疾临床诊断，因为它消除了抽血所涉及的职业危害，从而有助于减少不必要地使用抗疟药物。总的来说，它有可能显著影响流行地区95%以上的临床疟疾的诊断和治疗方式，并推动目前全球努力实现世界卫生组织规定的在所有发热病例治疗前进行疟疾的家庭或护理点检测。由于它基于与当前RDT相同的平台，因此该测试可以轻松集成到当前的医疗保健结构中，为大多数流行国家的公共卫生提供显着益处。目前尚无此类测试。

This Small Business Innovation Research Phase I project aims to develop a bivalent monoclonal antibody using novel Plasmodium falciparum (Pf) and P. vivax (Pv) proteins shed in the urine of febrile malaria patients. Using a bioinformatics approach, we will create, score, and select in silico-generated recombinants of natural antigen variants designed to express mosaics that maximize the inclusion of common potential in one structure and minimize the inclusion of rare epitopes. Antigenic properties of the recombinant antigens are validated by indirect ELISA using panels of well-characterized sera from apparently healthy individuals and clinical Pf and Pv malaria patients. The utility of the recombinant antibodies are evaluated in a dipstick test using a range of clinical urine samples from Pf/Pv endemic regions. Our overall objective is to develop a simple one-step urine-based dipstick test for the simultaneous but specific diagnosis of clinical Pf and/or Pv malaria. The broader impact/commercial potential of this project relates to the development of a broad-based one step urine test for home-based or point-of-care diagnosis of clinical Pf and/or Pv malaria in persons with fever. The test will potentially provide a reliable tool to differentiate between symptomatic and asymptomatic disease, and provide better treatment options to those in need. It will potentially offer wider acceptability of clinical malaria diagnosis in endemic regions, especially in remote settings and in places where mixed infections frequently occur by obviating the occupational hazards involved with phlebotomy, thus helping to reduce the unnecessary use of antimalarial drugs. Overall, it has the potential to markedly impact the way over 95% of all clinical malaria is diagnosed and treated in endemic regions, and drive the current global effort towards home-based or point-of-care testing for malaria mandated by the World Health Organization prior to treatment in all cases of fever. Since it is based on the same platform as current RDTs, this test can be easily integrated into current healthcare structures to provide significant benefits to public health in most endemic countries. No such test is currently available.