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

Abstract

The 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 postattachment 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.

Effects of Oregano Essential Oil on IgA+, IgG+, and IgM+ Cells in the Jejunum of Castrated Holstein Bulls

“…IgM is the largest molecular weight immunoglobulin and exists mainly in pentamer form [10]. It can exert immune effects, such as bacteriolytic effects and neutralising viruses by activating complement [11], and its agglutination and haemolysis with complement participation are 500-1000 times higher than those of IgG, making it a highly potent antibody. Therefore, IgA, IgG, and IgM play important roles in jejunal immunity.…”