Dual blockages of a broad and potent neutralizing IgM antibody targeting GH loop of EV‐As

Abstract

AbstractThe reported enterovirus A 71 (EVA71) vaccines and immunoglobin G (IgG) antibodies have no cross‐antiviral efficacy against other enterovirus A (EV‐A) which caused hand, foot and mouth disease (HFMD). Here we constructed an IgM antibody (20‐IgM) based on our previous discovery to address the resistance encountered by IgG‐based immunotherapy. Although binding to the same conserved neutralizing epitope within the GH loop of EV‐As VP1, the antiviral breath and potency of 20‐IgM are still higher than its parental 20‐IgG1. The 20‐IgM blocks the interaction between the EV‐As and its receptors, scavenger receptor class B, member 2 (SCARB2) and Kringle‐containing transmembrane protein 1(KREMEN1) of the host cell. The 20‐IgM also neutralizes the EV‐As at the post‐attachment stages, including postattachment neutralization, uncoating and RNA release inhibition after internalization. Mechanistically, the dual blockage effect of 20‐IgM is dependent on both a conserved site targeting and high affinity binding. Meanwhile, 20‐IgM provides cross‐antiviral efficacy in EV‐As orally infected neonatal ICR mice. Collectively, 20‐IgM and its property exhibit excellent antiviral activity with a dual‐blockage inhibitory effect at both the pre‐ and post‐attachment stages. The finding enhances our understanding of IgM‐mediated immunity and highlights the potential of IgM subtype antibodies against enterovirus infections.