The worldwide burden of malaria disease is profound. Infection with the Plasmodium falciparum species has the most devastating effect, causing the death of nearly one million African children each year. Even so, malaria control is a realistic goal, based on two lines of evidence: 1) natural immunity emerges with age in persons repeatedly exposed to the parasite;and 2) pre-erythrocytic vaccine candidates can reduce incidence of clinical disease. Currently, a major hindrance in achieving this goal is the lack of a deep understanding of the mechanisms of immune protection against malaria that can guide rational vaccine design. In this project we propose two Specific Aims that will use a comprehensive systems biology approach to broaden the immunologic knowledge base of malaria by investigating naturally acquired immunity and vaccine-induced protection in African populations living in malaria-endemic areas.
In Aim 1, we will determine the distinct immune signatures associated with control of parasitemia and acquired immunity in Ugandan children and adults.
In Aim 2, we will partner with investigators in the conduct of a phase III RTS,S/AS01E vaccine licensure trial to define the immunogenicity and correlates of vaccine protection in young children. As relatively new investigators in this exciting research field, we will contribute our collective expertise in the design and conduct of comprehensive immunologic studies in large-scale international vaccine studies in concert with advanced systems biology, bioinformatics and network analyses. Our Seattle colleagues with recognized leadership in the malaria field will guide our efforts, and we can efficiently build upon findings in the two interactive projects. We envision these investigations will lend significant insight into the innate and adaptive immune mechanisms that control malaria infection.

Public Health Relevance

Forty percent of annual public health expenditures in sub-Saharan Africa is spent on the 300 million cases of acute malaria which result in one million deaths, mostly of children under five. The concomitant high costs exacted by this disease also restrain economic development. Our investigations will lend significant insight toward the development of a vaccine as part of a strategy to eradicate this scourge.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-QV-I)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Seattle Biomedical Research Institute
United States
Zip Code
Finak, Greg; Frelinger, Jacob; Jiang, Wenxin et al. (2014) OpenCyto: an open source infrastructure for scalable, robust, reproducible, and automated, end-to-end flow cytometry data analysis. PLoS Comput Biol 10:e1003806
McDavid, Andrew; Dennis, Lucas; Danaher, Patrick et al. (2014) Modeling bi-modality improves characterization of cell cycle on gene expression in single cells. PLoS Comput Biol 10:e1003696
Finak, Greg; McDavid, Andrew; Chattopadhyay, Pratip et al. (2014) Mixture models for single-cell assays with applications to vaccine studies. Biostatistics 15:87-101
Finney, Olivia C; Keitany, Gladys J; Smithers, Hannah et al. (2014) Immunization with genetically attenuated P. falciparum parasites induces long-lived antibodies that efficiently block hepatocyte invasion by sporozoites. Vaccine 32:2135-8
Huang, Yunda; Gottardo, Raphael (2013) Comparability and reproducibility of biomedical data. Brief Bioinform 14:391-401
McDavid, Andrew; Finak, Greg; Chattopadyay, Pratip K et al. (2013) Data exploration, quality control and testing in single-cell qPCR-based gene expression experiments. Bioinformatics 29:461-7