Designing a diversity-covering multiantigen multi-strain malaria vaccine

首席研究员是一位分子流行病学家，他的总体目标是成为一种独立的疟疾 疫苗专家。这个职业发展奖的目标是设计一种覆盖多样性的多抗原多 培育疟疾疫苗，以提供对疟疾感染的超越菌株的保护。 候选人：瓦塔拉博士是美国疾病控制与预防研究所疟疾研究部的副研究员 马里兰大学医学院全球卫生(IGH)。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、统计遗传学和人口方面的专业知识 遗传学为他进行拟议的研究做好了准备。为了实现他长期的职业发展目标 成为疟疾疫苗学的独立研究员，瓦塔拉博士的职业发展计划将包括 培训内容：1)免疫学、蛋白质设计和疫苗学；2)生物信息学；3)写作、交流和 伦理道德。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。瓦塔拉医生的 初级导师Marcelo Sztein博士是一位有成就的免疫学家，对评估 对疫苗的免疫反应。他培养了成功的独立调查人员。瓦塔拉医生的联合- 导师克里斯托弗·普洛博士是一位疟疾专家，他在培训独立研究人员方面有过往记录。Dr。 瓦塔拉的顾问委员会包括传染病疫苗专家彼得·霍特斯博士、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， 基因组学专家Joana Silva博士，IGH主任兼疫苗试验和领导凯瑟琳·Neuzil博士 政策，以及DMR主任Miriam Laufer博士，他是一位经验丰富的疟疾翻译研究员和 忠诚的导师。除了他的委员会的指导外，瓦塔拉博士还将在一个强大的 IGH的跨学科研究环境，这是一所致力于支持年轻教师的机构。 研究。尽管接种疫苗是消除疟疾的一种非常有希望的方法，但没有 商业上可用的疟疾疫苗。这项拟议的探索性研究旨在评估沙棘的遗传多样性。 疟疾抗原、MSP5、SPECT1和Pfs48/45，以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、南美洲和亚洲进行的完整疟疾调查中收集的样本。最多的 这些抗原的流行单倍型将优先用于进一步评估。在目标2中，抗原变体 经过这一过程的优先顺序将在杆状病毒和毕赤酵母表达系统中表达，并 多克隆抗体产生了我的免疫小鼠。主要的抗原变体将通过一个阶段进行评估- 特异性功能测定。到拟议活动结束时，和平倡议将有一个既定的渠道，以确定 并表达候选疫苗和可能为进一步临床前开发做好准备的特定抗原。

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.