Main Conference Day 3Wednesday, 16 December 2026 - PT (Pacific Time, GMT-08:00)

The protective L9 antibody preferentially recognizes the ‘NVDP’ minor repeat motif in Plasmodium falciparumcircumsporozoite protein (CSP), with lower affinity to the ‘NANP’ major repeat motif. However, strain variation in NVDP minor repeat number and spacing may limit breadth across strains. Using directed evolution and yeast display, we discovered a panel of affinity-improved L9 variants. Among these, L9_yd19 conferred improved protection against diverse chimeric CSP variants while preserving potency against the more common strain 3D7’s CSP architecture. Cryo-EM revealed distinct dual homotypic antibody interfaces, with the new interface outlining a structural mechanism to form higher-order Fab assemblies and broaden protection across diverse PfCSP repeat architectures.