The Mucosal Vaccine Adjuvant LT(R192G/L211A) or dmLT

mSphere. 2018 Jul 25;3(4):e00215-18. doi: 10.1128/mSphere.00215-18.

Abstract

Perhaps the best-studied mucosal adjuvants are the bacterially derived ADP-ribosylating enterotoxins. This adjuvant family includes heat-labile enterotoxin of Escherichia coli (LT), cholera toxin (CT), and mutants or subunits of LT and CT. These proteins promote a multifaceted antigen-specific response, including inflammatory Th1, Th2, Th17, cytotoxic T lymphocytes (CTLs), and antibodies. However, more uniquely among adjuvant classes, they induce antigen-specific IgA antibodies and long-lasting memory to coadministered antigens when delivered mucosally or even parenterally. The purpose of this minireview is to describe the general properties, history and creation, preclinical studies, clinical studies, mechanisms of action, and considerations for use of the most promising enterotoxin-based adjuvant to date, LT(R192G/L211A) or dmLT. This review is timely due to completed, ongoing, and planned clinical investigations of dmLT in multiple vaccine formulations by government, nonprofit, and industry groups in the United States and abroad.

Keywords: adjuvant; dmLT; mucosal vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adjuvants, Immunologic / genetics*
  • Adjuvants, Immunologic / metabolism*
  • Administration, Mucosal
  • Bacterial Toxins / genetics*
  • Bacterial Toxins / metabolism*
  • Enterotoxins / genetics*
  • Enterotoxins / metabolism*
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism*
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Vaccines / administration & dosage
  • Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • Bacterial Toxins
  • Enterotoxins
  • Escherichia coli Proteins
  • Mutant Proteins
  • Protein Subunits
  • Vaccines
  • heat-labile enterotoxin, E coli