Oral Presentation 16th Lorne Infection and Immunity 2026

Structural and Antigenic Diversity of Emerging Japanese Encephalitis Virus Genotypes (132540)

Morgan Freney 1 , Yu Shang Low 1 , Connor Scott 1 , Summa Bibby 1 , Alberto Ortiz Amarilla 1 , Benjamin Liang 1 , Natalee Newton 1 , Jessica Harrison 1 , Mahali Morgan 1 , Roy Hall 1 , Jody Hobson-Peters 1 , Daniel Watterson 1 , Naphak Modhiran 1
  1. The School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane St Lucia, QLD, Australia

Japanese encephalitis virus (JEV) comprises five genotypes (GI-GV), with emerging GIV and GV displaying significant genetic divergence from the GIII-derived vaccine strain. Using single-particle cryogenic electron microscopy (cryo-EM) and a chimeric virus platform, we determined near-atomic resolution structures of the virion surface architecture for all five JEV genotypes to allow mapping of the antigenic differences across all genotypes for the first time. To understand how genotype specific mAbs differentially recognise diverse JEV genotypes, we used cryo-EM to resolve the epitope of a potent but genotype restricted neutralising antibody and identified a complex quaternary epitope spanning three envelope protein monomers, with specific residue changes in GIV and GV contributing to immune escape. Complementing these structures, we also demonstrate that sera from GIII-vaccinated individuals show significantly reduced neutralisation of GIV and GV viruses. This comprehensive structural and antigenic analysis establishes a molecular basis for differential vaccine efficacy and provides a framework for developing broader protective vaccines against emerging JEV genotypes. These findings have clear public health implications, particularly given the recent emergence and establishment of JEV in Australia.