Structural analysis of the specificity of three neutralising human monoclonal antibodies against poliovirus

Abstract Despite a global eradication programme, pathogenic polioviruses (PVs) still circulate, dictating a need for improved vaccines, therapeutics and diagnostics. Understanding their antigenic properties has been based largely on studies in mice. Here we study three human monoclonal antibodies specific for the native conformation and either PV1, 2 or 3, determining high-resolution structures of complexes with virus-like particles. The anti-PV1 and anti-PV2 Fabs bind around the icosahedral 3-fold axes, whilst the anti-PV3 Fab binds the canyon. We reveal the basis of serotype specificity and discrimination between native and expanded antigenic states. The anti-PV3 antibody partly penetrates the canyon and makes numerous serotype specific interactions on the south canyon face, distinguishing it from a pan-serotype and pan-antigenic state PV antibody. These structures show that human antibodies often span more than one classical antigenic site and can bind deeper crevices than murine antibodies, expanding our understanding of the antigenic landscape of PV capsids and potentially informing the design of better reagents, antivirals and vaccines against PV.