Fig. 1

Immune response to vaccination and potential for targeting hallmarks of aging to improve age-related deficits in vaccine responses. Both innate and adaptive immune responses are induced by vaccination, which commonly occur via intramuscular injection. Adjuvants are sometimes included in vaccines to enhance immunogenicity. The vaccine is injected into muscle. Antigen is taken up by dendritic cells (DCs) and activate pattern recognition receptors (PRRs). DCs secrete chemokines that recruit other monocytes from the blood, where they migrate to the site of injection, and then uptake antigen and differentiate. Antigen experienced innate immune cells migrate to the lymph node and present antigen on Major Histocompatibility Complexes (MHC) to activate naïve T cells through T cell receptors (TCRs). Both CD4 and CD8 T cells can respond depending on the type of vaccination and MHC presentation. CD4 T cells will differentiate into various T helper subsets, where T follicular helper cells (Tfh) provide help to B cells. B cells in the lymph node can respond to both antigen and T cell help, which leads to maturation and proliferation into memory B cells and plasma cells. Short-lived plasma cells generate antibodies specific to vaccine antigen which circulate systemically. Long-lived plasma cells reside in the bone marrow and provide long-lasting antibody protection. These vaccine-induced cellular interactions are highly coordinated and depend on proper microenvironment milieu and specific immune cell functions and signaling. It is well known that various areas of the immune response to vaccination are impaired with aging as detailed in this review. We propose that targeting different hallmarks of aging can modulate the tightly coordinated responses to improve overall vaccine responses in older adults. Figure created with Biorender.com