Structural and genetic basis for broad antibody recognition of a protective epitope on orthomarburgvirus GP2.

Orthomarburgviruses are the etiological agents of human Marburg virus disease, with case fatality rates reaching up to 90%. Of the limited known targets for protective antibodies on the orthomarburgvirus surface glycoprotein (GP), the GP2 wing region is undefined structurally, and its recognition by antibodies is poorly understood. We report a comprehensive genetic and structural analysis of four independent broadly reactive antibody lineages that target a common epitope within the GP2 wing, including macaque antibodies CM10, CM11.1, and CM12.1 and murine antibody 30G4. Co-crystal structures reveal the recognition of conserved structural determinants within the wing by all four antibodies. Immunogenetic analyses uncover common antibody sequence signatures that underlie interactions with the wing, leading in some cases to nearly identical modes of antibody binding. Our study advances the structural understanding of the GP2 wing protective region and defines conserved immunogenetic and structural features for broad antibody recognition, informing the development of vaccines and antibody countermeasures.