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.

PROJECT NARRATIVE Although vaccination is the control measure that has had the greatest impact on past disease eradication efforts, malaria vaccine development has been hampered by antigenic diversity. By using a diversity coverage approach, I expect to select variants of malaria antigens to be included in a future broadly cross-protective multi-variant, multi-protein malaria vaccine. While conducting this work, I will acquire knowledge that will allow me to become an independent malaria vaccine developer.