Recent advances in nontoxic Escherichia coli heat-labile toxin and its derivative adjuvants

Expert Rev Vaccines. 2016 Nov;15(11):1361-1371. doi: 10.1080/14760584.2016.1182868. Epub 2016 May 12.

Abstract

The nontoxic heat-labile enterotoxin (LT) of Escherichia coli and the B subunit of LT (LTB) have been extensively studied as potent vaccine adjuvants. Areas covered: This review covers the area of enterotoxin based vaccine adjuvant and summarizes the development of nontoxic LT mutant (mLT) and LTB and their potency as oral, parenteral and injection adjuvants. Recent evidences indicated that the mechanism of LTB adjuvanticity was to enhance the turnover of dendritic cells (DCs) in spleen and increase DCs capacity to perform as antigen presentation cells (APCs) encountered with T cells. LTB also induces B and T cells clustering and delay/arrest in T-cell division following endocytosis or B-cell receptor (BCR) uptaking of antigen in a ganglioside-mediated manner. Expert commentary: It is pointed out that the immunogenicity of LTB (or LT) is more important than the receptor binding property (or ADP-ribosylation activity) for the adjuvanticity of LT toxoid. The immunogenicity of LTB (or LT) might confer unknown characteristics to maintain LT toxoid adjuvanticity.

Keywords: ADP-ribosylation; Heat-labile enterotoxin; adjuvant; immune; nontoxic; vaccine.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • B-Lymphocytes / immunology
  • Bacterial Toxins / administration & dosage*
  • Bacterial Toxins / genetics
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Enterotoxins / administration & dosage*
  • Enterotoxins / genetics
  • Escherichia coli Proteins / administration & dosage*
  • Escherichia coli Proteins / genetics
  • Humans
  • Recombinant Proteins / administration & dosage
  • T-Lymphocytes / immunology
  • Toxoids / administration & dosage*
  • Toxoids / genetics

Substances

  • Adjuvants, Immunologic
  • Bacterial Toxins
  • Enterotoxins
  • Escherichia coli Proteins
  • Recombinant Proteins
  • Toxoids
  • heat-labile enterotoxin, E coli