Journal of Vaccine Research, 2025, Vol.15, No.1, 10-22 http://medscipublisher.com/index.php/jvr 13 4 Host-Related Factors 4.1 The influence of age and immune senescence on vaccine effectiveness As people age, their immune function gradually deteriorates. This phenomenon is called immune senescence, which affects both the innate and acquired immune capabilities of the human body. This will lead to a reduction in the types and functions of B cells and T cells, a decline in their ability to deliver antigens, and may also cause long-term mild inflammation. All these will result in a weakened immune response in the elderly after vaccination (Figure 1) (Pereira et al., 2020; Hou et al., 2024). Therefore, even if they have been vaccinated, the elderly still find it difficult to obtain long-lasting and effective protection and are more vulnerable to infectious diseases (Pera et al., 2015; Oh et al., 2019; Crooke et al., 2019; Allen et al., 2020; Chen et al., 2024). Figure 1 The characteristics of changes in immunosenescence at the systematic, cellular, and molecular levels in elderly individuals (Adopted from Hou et al., 2024) Image caption: The generation and maintenance of protective immunity induced by vaccination are weakened; The cGASSTING, NLRP3 and NF-κB signaling pathways were upregulated, leading to chronic inflammation; Meanwhile, the expression of MHC, TLRs, and costimulatory molecules on APCs is reduced, leading to reduced migration to the lymph node, internalization, and antigen presentation ofAPCs; Tcells have low expression of TCRs and costimulatory molecules, but high expression of PD-1, which leads to reduced Tcell stimulation. At the molecular level, there are mainly compromised autophagy and telomere attrition; STING stimulator of interferon genes, cGAS cyclic GMP-AMP synthase, NLRP3 NOD-, LRR-and pyrin domain-containing protein 3, NF-κBnuclearfactorkappa-light-chain-enhancer of activated B cells, SASP senescence-associated secretory phenotype, APC antigen-presenting cell, MHCmajorhistocompatibilitycomplex,TCRTcell receptor, TLR toll-like receptor, PD-1 programmed death receptor-1, ATG5 autophagy-related 5, ATG7 autophagy-related 7 (Created with Adobe illustrator) (Adopted from Hou et al., 2024) In reality, vaccines like influenza, pneumonia and COVID-19 are not very effective in the elderly (Allen et al., 2020). Nowadays, methods such as adding auxiliary components, increasing vaccine doses, and adjusting vaccination times are commonly used to improve the situation, but the effects are limited (Pereira et al., 2020; Chen et al., 2024; Hou et al., 2024). Scientists are still studying the principle of immunosenescence, hoping to develop vaccines that are more suitable for the elderly (Crooke et al., 2019; Oh et al., 2019; Hou et al., 2024). 4.2 Genetic factors and individual differences in immune responses Everyone's genes are different. For instance, HLA types and other genetic differences related to immunity can all lead to different responses after vaccination. These genetic differences can affect the process of antigen delivery by cells, alter the number of immune cells, and also influence the production of cytokines, thereby affecting the intensity, effectiveness and duration of the immune response. Scientists use systems biology methods to study the relationship between genetic and molecular characteristics and vaccine responses, especially in the cases of aging and weakened immune function (Poland et al., 2014; Crooke et al., 2019).
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