Aging is characterized by a general decline in a range of physiological functions, with a consequent
increase in the risk of developing a variety of chronic diseases and geriatric syndromes. Additionally, increasing
age is accompanied by a progressive decline in both innate and acquired immune system, referred to as immunosenescence.
This impaired ability to mount an efficient immune response after exposure to microorganisms or
vaccines represents a major challenge in acquiring protection against pathogens in aging. Therefore, there is still a
great need for vaccines that are tailored to optimally stimulate the aged immune system, thus promoting more
successful aging. Various strategies can be used to improve vaccine efficacy in old people. Despite this, metaanalyses
have clearly shown that the magnitude of protection obtained remains lower in older adults. Recent
studies show that stimulation of Toll-like receptors, using stimulatory ligands, can enhance vaccine efficacy by a
number of mechanisms, including the activation of innate immune cells and the consequent production of inflammatory
cytokines. Therefore, a possible strategy for more effective vaccination in the older population is the
triggering of multiple TLRs, using a combined adjuvant for the synergistic activation of cellular immunity. Preliminary
in vitro data suggest that in humans the presence of multiple TLR agonists can result in the greater
stimulation of antigen-specific immune responses in immune cells both in the young healthy and in the immune
senescent older donors. These data suggest that appropriately selected combinations of TLR agonists could enhance
the efficacy of vaccination mediated immunity in older people.