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

• Published in: Expert opinion on biological therapy Vol. 4; no. 7; p. 1129
• Main Authors: Baldridge, Jory R, McGowan, Patrick, Evans, Jay T, Cluff, Christopher, Mossman, Sally, Johnson, David, Persing, David
• Format: Journal Article
• Language: English
• Published: England 01.07.2004
• Subjects: 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
• ISSN: 1744-7682
• DOI: 10.1517/14712598.4.7.1129

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.