Oral Presentation 51st Lorne Proteins Conference 2026

Structural and Antigenic Diversity of Emerging Japanese Encephalitis Virus Genotypes  (132855)

Morgan E Freney 1 , Yu Shang Low 1 , Connor A P Scott 1 , Summa Bibby 1 , Alberto A Amarilla 1 , Benjamin Liang 1 , Natalee D Newton 1 , Jessica J Harrison 1 , Mahali S Morgan 1 , Roy A 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) expansion and emergence into new regions poses a growing public health challenge globally. Comprising five distinct genotypes (GI-GV), emerging GIV and GV display significant genetic divergence from the GIII-derived vaccine strain. Using single-particle cryogenic electron microscopy (cryo-EM) and a chimeric virus platform, we determine near-atomic resolution structures (<3.7Å) of the virion surface architecture for all five JEV genotypes to allow mapping of the antigenic differences across all genotypes for the first time. Complementing these structures, we also demonstrate that human sera from GIII-vaccinated individuals exhibits significantly reduced neutralisation of GIV and GV viruses and neutralising monoclonal antibodies (mAb) differentially bind and inhibit GIV and GV. To elucidate the structural basis for genotype-specific recognition, we used cryo-EM to resolve the epitope of a potent but genotype restricted neutralising antibody. Revealing a complex quaternary epitope spanning three envelope protein monomers, with specific residue changes in GIV and GV contributing to immune escape. 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.