Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents

Expert Opin Biol Ther. 2004 Jul;4(7):1129-38. doi: 10.1517/14712598.4.7.1129.

Abstract

Toll-like receptor (TLR) agonists are being developed for use as vaccine adjuvants and as stand-alone immunomodulators because of their ability to stimulate innate and adaptive immune responses. Among the most thoroughly studied TLR agonists are the lipid A molecules that target the TLR4 complex. One promising candidate, monophosphoryl lipid A, which is a derivative of lipid A from Salmonella minnesota, has proven to be safe and effective as a vaccine adjuvant in > 120,000 human doses. A new class of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4-phosphates (AGPs), have been engineered specifically to target human TLR4 and are showing promise as vaccine adjuvants and as monotherapeutic agents capable of eliciting nonspecific protection against a wide range of infectious pathogens. In this review, the authors provide an update of the preclinical and clinical experiences with the TLR4 agonists, MPL (Corixa Corporation) adjuvant and the AGPs.

Publication types

  • Review

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use*
  • Aged
  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / immunology
  • Bacterial Infections / prevention & control
  • Bacterial Vaccines / administration & dosage
  • Child
  • Clinical Trials as Topic
  • Drug Design
  • Drug Evaluation, Preclinical
  • Female
  • Glycolipids / chemistry
  • Glycolipids / immunology
  • Glycolipids / therapeutic use
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use*
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives*
  • Lipid A / chemistry
  • Lipid A / immunology
  • Lipid A / pharmacology
  • Lipid A / therapeutic use
  • Lymphocyte Activation / drug effects
  • Male
  • Membrane Glycoproteins / agonists*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Protozoan Infections / drug therapy
  • Protozoan Infections / prevention & control
  • Receptors, Cell Surface / agonists*
  • Receptors, Cell Surface / physiology
  • Respiratory Syncytial Virus Infections / drug therapy
  • Respiratory Syncytial Viruses / drug effects
  • Respiratory Syncytial Viruses / physiology
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Viral Vaccines / administration & dosage
  • Virus Diseases / drug therapy*
  • Virus Diseases / immunology
  • Virus Diseases / prevention & control
  • Virus Replication / drug effects

Substances

  • Adjuvants, Immunologic
  • Antiviral Agents
  • Bacterial Vaccines
  • Glycolipids
  • Immunologic Factors
  • Lipid A
  • Membrane Glycoproteins
  • RC 527
  • RC529
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Viral Vaccines
  • monophosphoryl lipid A