Correlates of GLA family adjuvants' activities

Steven G Reed; Darrick Carter; Corey Casper; Malcolm S Duthie; Christopher B Fox

doi:10.1016/j.smim.2018.10.004

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.

Authors

Steven G Reed¹, Darrick Carter², Corey Casper³, Malcolm S Duthie⁴, Christopher B Fox⁵

Affiliations

¹ Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102 USA. Electronic address: [email protected].
² Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102 USA. Electronic address: [email protected].
³ Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102 USA. Electronic address: [email protected].
⁴ Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102 USA. Electronic address: [email protected].
⁵ Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102 USA. Electronic address: [email protected].

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

Grants and funding

R01 AI025038/AI/NIAID NIH HHS/United States