Understanding cross-reactive immunity to Japanese encephalitis virus (360G-Wellcome-205228_Z_16_Z)

The flavivirus Japanese encephalitis (JE) virus (JEV) causes devastating disease in thousands of Southeast Asian children every year. The sequence of flavivirus infection and cross-reactivity are important determinants of immunopathogenesis, but these phenomena are understudied outside dengue. A deeper understanding of immunological cross-reactivity will underpin development of next-generation flavivirus vaccines and novel therapeutic approaches. The sequence of flavivirus infection is hard to confirm in endemic areas, and initial exposure usually occurs in early childhood—this makes field studies difficult and alternative approaches are urgently required.The key goals of this Fellowship are:1. Develop a human experimental model of JEV infection using live JE vaccine in flavivirus-naïve adult volunteers and previously yellow fever vaccinated subjects.2. Identify conserved epitopes between flaviviruses that may serve as targets for novel vaccines and therapeutics.3. Train in advanced B cell immunology techniques, including the development of human JEV monoclonal antibodies and flavivirus B cell epitope mapping.This programme of work will provide new insights into JE pathogenesis, further elucidate fundamental principles of flavivirus immunology and provide new tools to develop better therapeutics for this important and understudied disease. The training opportunities will help me develop as a leader in viral immunology and experimental medicine.