The Stimulatory Effect of the TLR4-mediated Adjuvant Glucopyranosyl Lipid A Is Well Preserved in Old Age

Biogerontology. 2016 Feb;17(1):177-87. doi: 10.1007/s10522-015-9576-x. Epub 2015 May 9.

Abstract

Many subunit vaccines require adjuvants to improve their limited immunogenicity. Various adjuvant candidates targeting toll-like receptors (TLRs) are currently under development including the synthetic TLR4 agonist glucopyranosyl lipid A (GLA). GLA has been investigated in the context of influenza vaccine, which is of particular importance for the elderly population. This study investigates the effect of GLA on antigen-presenting cells from young (median age 29 years, range 26-33 years) and older (median age 72 years, range 61-78 years) adults. Treatment with GLA efficiently increases the expression of co-stimulatory molecules on human monocyte-derived dendritic cells (DC) as well as on ex vivo myeloid DC. Expression of co-stimulatory molecules is less pronounced on ex vivo monocytes. Production of pro-inflammatory cytokines (IL-6, TNF-α, IL-12) as well as of the anti-inflammatory cytokine IL-10 is induced in monocyte-derived DC. In PBMC cultures myeloid DC and to an even greater extent monocytes produce TNF-α and IL-6 after stimulation with GLA. Production of IL-12 can also be observed in these cultures. There are no age-related differences in the capacity of GLA to induce expression of co-stimulatory molecules or production of cytokines by human antigen-presenting cells. Therefore, TLR4 agonists like GLA are particularly promising candidates as adjuvants of vaccines designed for elderly individuals.

Keywords: Adjuvant; Ageing; Antigen-presenting cells; Elderly; TLR 4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology*
  • Cells, Cultured
  • Cytokines / immunology*
  • Female
  • Glucosides / administration & dosage*
  • Glucosides / immunology
  • Humans
  • Lipid A / administration & dosage*
  • Lipid A / immunology
  • Male
  • Middle Aged
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptor 4 / immunology*
  • Treatment Outcome
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Glucosides
  • Lipid A
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Vaccines, Subunit
  • glucopyranosyl lipid-A