Correlates of GLA family adjuvants' activities

Semin Immunol. 2018 Oct:39:22-29. doi: 10.1016/j.smim.2018.10.004. Epub 2018 Oct 23.

Abstract

Lipopolysaccharide (LPS) is a well-defined agonist of Toll-like receptor (TLR) 4 that activates innate immune responses and influences the development of the adaptive response during infection with Gram-negative bacteria. Many years ago, Dr. Edgar Ribi separated the adjuvant activity of LPS from its toxic effects, an effort that led to the development of monophosphoryl lipid A (MPL). MPL, derived from Salmonella minnesota R595, has progressed through clinical development and is now used in various product-enabling formulations to support the generation of antigen-specific responses in several commercial and preclinical vaccines. We have generated several synthetic lipid A molecules, foremost glucopyranosyl lipid adjuvant (GLA) and second-generation lipid adjuvant (SLA), and have advanced these to clinical trial for various indications. In this review we summarize the potential and current positioning of TLR4-based adjuvant formulations in approved and emerging vaccines.

Keywords: Adjuvant; Formulation; Monophosphoryl lipid A; Toll-like receptor 4; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Alum Compounds / chemistry
  • Alum Compounds / pharmacology*
  • Animals
  • Glucosides / chemistry
  • Glucosides / pharmacology*
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Humoral / drug effects
  • Immunogenicity, Vaccine*
  • Leishmaniasis / immunology
  • Leishmaniasis / parasitology
  • Leishmaniasis / prevention & control
  • Leprosy / immunology
  • Leprosy / parasitology
  • Leprosy / prevention & control
  • Lipid A / analogs & derivatives*
  • Lipid A / chemistry
  • Lipid A / pharmacology
  • Liposomes / administration & dosage
  • Liposomes / chemistry
  • Liposomes / immunology
  • Malaria / immunology
  • Malaria / parasitology
  • Malaria / prevention & control
  • Mice
  • Schistosomiasis / immunology
  • Schistosomiasis / parasitology
  • Schistosomiasis / prevention & control
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / microbiology
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology
  • Tuberculosis / immunology
  • Tuberculosis / microbiology
  • Tuberculosis / prevention & control*
  • Vaccines / administration & dosage
  • Vaccines / chemistry
  • Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Glucosides
  • Lipid A
  • Liposomes
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Vaccines
  • glucopyranosyl lipid-A
  • monophosphoryl lipid A