title: The stimulatory effect of the TLR4-mediated adjuvant glucopyranosyl lipid A is well preserved in old age.
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.
authors.affiliation: Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Weinberger
authors.affiliation: Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Joos
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Ave E #400, Seattle, WA, 98102, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Ave E #400, Seattle, WA, 98102, USA.
authors.forename: Rhea
authors.initials: R
authors.lastname: Coler
authors.affiliation: Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, 6020, Innsbruck, Austria. beatrix.grubeck@uibk.ac.at.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000276:immunology*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D005960:Glucosides; D008050:Lipid A; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D022223:Vaccines, Subunit; C000608161:glucopyranosyl lipid-A
keywords: Adjuvant; Ageing; Antigen-presenting cells; Elderly; TLR 4