A DNA vaccine to prevent transmission of human malaria

预防人类疟疾传播的 DNA 疫苗

• 批准号: 7893555
• 负责人: Nirbhay Kumar
• 金额: $ 31.88万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-13 至 2012-09-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7893555
• 关键词: 6H,8H-3,4-dihydropyrimido(4,5-c)(1,2)oxazin-7-one; Animal Model; Antibodies; Antigen Targeting; Antigens; Aotus primate; Artificial Membranes; Back; Biological; Biological Assay; Blocking Antibodies; Clinical Trials; Culicidae; Cysteine; DNA Vaccines; Development; Drug Formulations; Electroporation; Epitopes; Evaluation; Goals; Gold; Human; Immune Sera; Immune response; Immunity; In Vitro; Individual; Infection; Life Cycle Stages; Lipids; Macaca mulatta; Malaria; Membrane; Methods; Modeling; National Center for Research Resources; Nature; Oocysts; Pan Genus; Parasites; Plasmids; Plasmodium falciparum; Proteins; Research; Serum; Staging; Testing; Transgenic Model; Transgenic Organisms; Vaccination; Vaccines; base; feeding; fertilization antigen; immunogenicity; in vivo; mouse model; nonhuman primate; parent grant; prevent; programs; public health relevance; research study; response; success; transmission process; transmission-blocking vaccine; vaccine delivery; vaccine development; vaccine evaluation; zygote

DESCRIPTION (provided by applicant): The current application is submitted in response to the notice number NOT-OD-058 entitled "Enabling RPGs to Leverage NCRR Center and Centers-like Programs". The research focus of the parent grant RO1AI0470889 is to develop a vaccine targeting human malaria. Transmission blocking vaccines (TBVs) against malaria are intended to induce immunity against the stages of the parasite that infect mosquitoes so that malaria transmission is reduced or halted. The target antigens include proteins synthesized in the gametocytes (pre-fertilization antigens, in P. falciparum: Pfs230 and Pfs48/45) and in the zygotes-ookinetes (post-fertilization antigens, in P. falciparum: Pfs25 and Pfs28) and the epitopes recognized by transmission blocking antibodies are cysteine-rich reduction-sensitive conformational in nature. Studies proposed in the parent grant were aimed at (1) identifying immunologically relevant domains in the pre- fertilization antigens, (2) optimizing the combination of pre- and post-fertilization antigens by vaccine formulation in cationic lipids and vaccine delivery by in vivo electroporation, (3) evaluating a candidate DNA vaccine by in vivo electroporation in nonhuman primates (Macaca mulatta) and testing the concept that immunity against pre-fertilization antigens can be maintained by boosting during natural infection using an Aotus model for P. falciparum infection. Moreover, the development of Pfs25 transgenic P. berghei will provide an approach for in vivo evaluation of human malaria TBV based on Pfs25, as compared to a standard in vitro membrane feeding assay. Since most vaccines go through immunogenicity and functional evaluation (wherever biologically feasible) in nonhuman primates, it is now proposed to revise the scope of the parent grant to develop transgenic nonhuman malaria parasite expressing Pfs25 which would then facilitate optimization and evaluation of Pfs25-based TBV. PUBLIC HEALTH RELEVANCE: Malaria causes more than 300 million infections worldwide. Our long term goal is to develop a vaccine to stop transmission of malaria. Research proposed in this application, in particular, will result in the development of a nonhuman primate model to test such human malaria transmission blocking vaccines.

描述（由申请人提供）：当前申请是针对NOT-OD-058的通知号提交的，标题为“启用RPG来利用NCRR中心和类似中心的程序”。父母赠款RO1AI0470889的研究重点是开发针对人类疟疾的疫苗。针对疟疾的传输阻断疫苗（TBV）旨在诱导感染蚊子的寄生虫​​阶段的免疫力，从而减少或停止疟疾的传播。靶抗原包括在配子细胞中合成的蛋白质（p. falciparum：PFS230和PFS48/45）和Zygotes-okinetes中合成的蛋白质（PFS230和PFS48/45）本质上，富含半胱氨酸的还原敏感构象。父母赠款中提出的研究的目的是（1）鉴定施肥抗原中的免疫学相关结构域，（2）通过疫苗配方在阳离子脂质中的疫苗配方优化前和后有效性抗原的组合，并通过在Vivo电载体中递送疫苗和疫苗的疫苗，（（3）评估VIV型（3）VIV（3）VIV（3）VIV（3） Mulatta）并测试了可以通过使用AOTUS模型来增强自然感染的抗原抗原的免疫力来维持对抗精神抗原的免疫力。此外，与标准的体外膜喂养测定法相比，PFS25转基因P. berghei的发展将提供一种基于PFS25的人类疟疾TBV评估的方法。由于大多数疫苗在非人类灵长类动物中都经过免疫原性和功能评估（无论在生物学上可行），因此现在提议修改父母赠款的范围，以开发转基因的非人类疟疾寄生虫表达PFS25，从而促进基于PFS25的基于PFS25的TBV。 公共卫生相关性：疟疾在全球引起超过3亿次感染。我们的长期目标是开发一种疫苗以停止疟疾的传播。特别是在本应用中提出的研究将导致发展非人类灵长类动物模型，以测试这种人类疟疾传播疫苗。