In Vivo Evaluation of Recombinantly Expressing M-Cell-Targeting Co1 Peptide Fused with VP1 of Enterovirus A71 Capsid

Abstract

Hand Foot Mouth disease, infected via the epithelium penetration of Enterovirus A71 (EVA71), causes neurological complications in children under five years old. VP1 is the most revealed protein capsid, gastric acid endurance, and immunogenic epitope expression of the EVA71. Co1 peptide is the ligand of the M cell, the main gate of the intestinal immune barrier, helping to transport antigens to the Gut-Associated Lymphoid Tissue in order to provoke mucosal immunity to secrete IgA. However, the present injectable vaccine of EVA71 only triggers IgG secretion but not IgA, which is ineffective for the prevention of mucosal-infected virus. Here we showed that the fusion of M-cell targeting Co1 peptide and VP1 protein, when orally gavaged, enhanced both IgA and IgG secretions. CO1-VP1 group’s antibody titer of fecal IgA had commenced on day three, the titer continued to increase doubly during the second week and fluctuated statically until the end of the experiment and were significantly higher than those of PBS and VP1 groups. Both types of antibody of the CO1-VP1 group had higher titer binding to VP1 antigen and EVA71 capsid than those of the VP1 group. The results provided the foundation for M cell-targeting oral vaccine development against EVA71 and for its clinical treatment of blood or neurological post-infection.

Graphical Abstract