Among the greatest achievements of modern medicine is the development of vaccines, but for many important diseases, such as HIV, tuberculosis and malaria, the production of safe and effective vaccines has been elusive. This is especially true for malaria, a disease that disproportionally affects children. An important first step in developing a rationally designed synthetic vaccine is the identification of antigens and their epitopes that are the actual determinants of immunological protection. The investigators propose to develop a new platform for the production of programmable proteome-scale peptide arrays on beads using a novel approach, whereby millions of peptides can be made deterministically and inexpensively on spectrally encoded microbeads. They will then conduct immunoassays on these beads to map epitopes across the entire proteome, using rodent malaria as a model system. The overall goal is to correlate mapped epitopes with actual protection from disease to inform the vaccine design process. This proposal embodies several major technological and conceptual innovations, and beyond vaccine design, this approach has the potential for broad impact on many fields of biomedical research, including cancer diagnostics, autoimmunity and allergy.