Prevention of Shiga toxin 1-caused colon injury by plant-derived recombinant IgA

Sci Rep. 2022 Oct 26;12(1):17999. doi: 10.1038/s41598-022-22851-4.

Abstract

Immunoglobulin A (IgA) is a candidate antibody for oral passive immunization against mucosal pathogens like Shiga toxin-producing Escherichia coli (STEC). We previously established a mouse IgG monoclonal antibody (mAb) neutralizing Shiga toxin 1 (Stx1), a bacterial toxin secreted by STEC. We designed cDNA encoding an anti-Stx1 antibody, in which variable regions were from the IgG mAb and all domains of the heavy chain constant region from a mouse IgA mAb. Considering oral administration, we expressed the cDNA in a plant expression system aiming at the production of enough IgA at low cost. The recombinant-IgA expressed in Arabidopsis thaliana formed the dimeric IgA, bound to the B subunit of Stx1, and neutralized Stx1 toxicity to Vero cells. Colon injury was examined by exposing BALB/c mice to Stx1 via the intrarectal route. Epithelial cell death, loss of crypt and goblet cells from the distal colon were observed by electron microscopy. A loss of secretory granules containing MUC2 mucin and activation of caspase-3 were observed by immunohistochemical methods. Pretreatment of Stx1 with the plant-based recombinant IgA completely suppressed caspase-3 activation and loss of secretory granules. The results indicate that a plant-based recombinant IgA prevented colon damage caused by Stx1 in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Caspase 3
  • Chlorocebus aethiops
  • Colon / metabolism
  • DNA, Complementary
  • Immunoglobulin A*
  • Immunoglobulin G
  • Mice
  • Mucins
  • Shiga Toxin 1
  • Shiga-Toxigenic Escherichia coli* / genetics
  • Vero Cells

Substances

  • Shiga Toxin 1
  • Immunoglobulin A
  • Caspase 3
  • DNA, Complementary
  • Immunoglobulin G
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Mucins