International Journal of Molecular Medical Science, 2025, Vol.15, No.4, 165-174 http://medscipublisher.com/index.php/ijmms 169 Figure 1 Inflammaging and chronic inflammatory conditions remodel the immune system by inducing a counteracting immunosuppression which promotes immunosenescence (Adopted from Salminen, 2022) Image caption: The immunosuppressive network involves MDSCs, Tregs, Bregs, DCregs, NKregs, NKT II cells, and type M2 macrophages. Subsequently, immunosuppression and an inefficient immune system disturb the efficacy of immune responses which increase the risk for cancers and chronic infections as well as decreasing the efficiency of vaccination and immunotherapy. Conversely, the increased immunosuppression associated with aging enhances transplantation tolerance. Abbreviation: Breg, regulatory B cell; DCreg, regulatory dendritic cell; MDSC, myeloid-derived suppressor cell; NKreg, regulatory natural killer cell; NKT II, type II natural killer T cell; Treg, regulatory T cell (Adopted from Salminen, 2022) 5 Ways to Make the Vaccine More Effective 5.1 Improve the vaccine itself Improving the "formula" of vaccines is a key approach to enabling elderly people with weak constitutions to have a better response to vaccines. Compared with ordinary doses of vaccines, high-dose vaccines (such as high-dose influenza vaccines) can trigger a stronger antibody response and better stimulate immunity in people with poor immunity (including the elderly and those with weakened immune systems) (Caldera et al., 2020). In addition, vaccines (multivalent vaccines) that can combat more types of viruses or bacteria can provide broader protection, which is particularly important for the elderly who are vulnerable to multiple pathogens (Hou et al., 2024). Improving "enhancers" (adjuvants) is another important direction. New enhancers (such as MF59, AS03, CpG ODN) have been proven to enhance the intensity and duration of the immune response in the elderly by activating the first line of defense of the human body more quickly and enabling immune cells to better recognize pathogens (Figure 2) (Bonam et al., 2017; Weinberg, 2018; Facciola et al., 2022). Customizing vaccine components and enhancers based on the characteristics of each individual's immune system (personalized vaccine design) is a new approach that is expected to maximize the efficacy of vaccines when the immune system ages and the body becomes weak (Li and Li, 2020; Hou et al., 2024). 5.2 Regulate the body's immunity By regulating the body's immune function, the efficacy of vaccines for elderly people with weak constitutions can be further enhanced. Supplementing nutrition, especially vitamin D, selenium, vitamin E and other nutrients that are often deficient in the elderly, has been proven to enhance the immune response after vaccination by supplementing these nutrients (deficiency may affect immunity) (Hou et al., 2024; Zhang, 2024). Improving the body's metabolic conditions (such as controlling blood sugar and blood lipids) and ensuring adequate protein intake are also crucial for maintaining the normal functioning of the immune system. Physical recovery and regular exercise have been proven to be beneficial for improving the function of antibodies and immune cells produced after vaccination, even for those with chronic diseases or suppressed immunity (Gualano et al., 2023). Anti-inflammatory treatments for long-term mild inflammation in the body are being studied to reduce the phenomenon of immune "braking" and improve vaccine responses. However, more research is needed to balance the relationship between controlling inflammation and effectively activating the immune system (Pereira et al., 2020; Hou et al., 2024).
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