Designing a diversity-covering multiantigen multi-strain vaccine

主要研究者是分子流行病学家，其总体目标是成为独立的疟疾 疫苗学家这个职业发展奖的目标是设计一个多样性覆盖的多抗原多， 菌株疟疾疫苗将提供针对疟疾感染的超越菌株保护。 候选人：瓦塔拉博士是疟疾研究所疟疾研究部（DMR）的研究助理。 全球健康（IGH）在马里兰州医学院。通过他的研究生和研究生 培训和经验，瓦塔拉博士在分子流行病学，统计遗传学和人口的专业知识 遗传学为他进行拟议的研究做好了准备。为了实现他的长期职业发展目标， 瓦塔拉博士的职业发展计划将包括 培训：1）免疫学，蛋白质设计和疫苗学; 2）生物信息学; 3）写作，沟通， 伦理关于领导力和实验室管理的教学也是瓦塔拉博士培训的一部分。 导师/环境：瓦塔拉博士组建了一个多学科团队来实现他的目标。瓦塔拉博士的 主要导师Marcelo Sztein博士是一位有成就的免疫学家，对评估 疫苗的免疫反应。他培养了成功的独立调查员。瓦塔拉博士的合作- 他的导师克里斯托弗·普洛维博士是一位疟疾专家，他有培训独立研究人员的记录。博士 瓦塔拉的顾问委员会包括彼得博士霍特兹，传染病疫苗学家，拉斐尔博士 蛋白质设计专家西蒙，著名疟疾分子流行病学家香农·塔卡拉·哈里森博士， 博士基因组学专家Joana Silva，IGH主任和疫苗试验领导人Kathleen Neuzil博士， 政策，以及DMR主任Miriam Laufer博士，一位经验丰富的转化疟疾研究人员和一位 忠诚的导师除了指导他的委员会，瓦塔拉博士将在一个强大的工作， IGH是一个致力于支持年轻教师的机构。 Research.尽管接种疫苗是消除疟疾的一种非常有希望的方法，但目前还没有 市售疟疾疫苗。这项探索性研究旨在评估 疟疾抗原、MSP 5、SPECT 1和Pfs 48/45来指导有效疫苗的设计。这项研究是 围绕两个目标构建。目的1检测恶性疟原虫疫苗抗原编码基因序列， 在非洲、南美洲和亚洲完成的疟疾调查中收集的样本。最 这些抗原的流行单倍型将优先用于进一步评价。在目标2中，抗原变体 通过该过程优先的蛋白质将在杆状病毒和巴斯德毕赤酵母表达系统中表达， 多克隆抗体产生了我的免疫小鼠。然后将通过一个阶段评估主要抗原变体- 特异性功能测定。在拟议活动结束时，PI将有一个既定的管道，以确定 并表达可用于进一步临床前开发的候选疫苗和特异性抗原。

The Principal Investigator is a molecular epidemiologist whose overall goal is to become an independent malaria vaccinologist. The goal of this career development award is to design a diversity-covering multi-antigen multi- strain malaria vaccine that will provide strain-transcending protection against malaria infection. Candidate: Dr. Ouattara is a Research Associate at the Division of Malaria Research (DMR) at the Institute for Global Health (IGH) at the University of Maryland School of Medicine. Through his graduate and post-graduate training and experience, Dr. Ouattara expertise in molecular epidemiology, statistical genetics, and population genetics prepares him to conduct the proposed research. To achieve his long-term career goal of developing into an independent researcher in malaria vaccinology, Dr. Ouattara's career development plan will include training in: 1) immunology, protein design, and vaccinology; 2) bioinformatics; 3) writing, communication, and ethics. Didactics on leadership and laboratory management are also part of Dr. Ouattara's training. Mentors/Environment: Dr. Ouattara has assembled a multidisciplinary team to achieve his goal. Dr. Ouattara's primary mentor, Dr. Marcelo Sztein, is an accomplished immunologist with a special interest in assessing immunological responses to vaccines. He has trained successful independent investigators. Dr. Ouattara's co- mentor, Dr. Christopher Plowe, a malaria expert who has a track-record of training independent researchers. Dr. Ouattara's advisory committee includes Dr. Peter Hotez, an infectious diseases vaccinologist, Dr. Raphael Simon, an expert in protein design, Dr. Shannon Takala Harrison, a renowned malaria molecular epidemiologist, Dr. Joana Silva, an expert in genomics, Dr. Kathleen Neuzil, the Director of IGH and leader in vaccine trials and policy, and Dr. Miriam Laufer, the Director of DMR, an experienced translational malaria researcher and a committed mentor. In addition to the mentorship of his committee, Dr. Ouattara will work in a strong interdisciplinary research environment at IGH, an institution that is committed to support young faculty members. Research. Even though vaccination is a highly promising approach for the elimination of malaria, there is no commercially available malaria vaccine. The proposed exploratory study aims to assess the genetic diversity of malaria antigens, MSP5, SPECT1, and Pfs48/45 to guide the design of an effective vaccine. The research is structured around two aims. Aim 1 examines P. falciparum vaccine antigen-encoding gene sequences in samples collected in completed malaria surveys performed in Africa, South America, and Asia. The most prevalent haplotypes of these antigens will be prioritized for further evaluation. In Aim 2, antigen variants prioritized through this process will be expressed in baculovirus and Pichia pastoris expression systems and polyclonal antibodies produced my immunizing mice. Leading antigen variants will then be evaluated by a stage- specific functional assay. By the end of the proposed activities, the PI will have an established pipeline to identify and express vaccine candidates and specific antigens that may be ready for further pre-clinical development.