The stimulatory effect of the TLR4-mediated adjuvant glucopyranosyl lipid A is well preserved in old age

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-alpha, 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-alpha 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.