Vaccine · Nov 14, 2026
Immunosenescence and vaccine adjuvants in older adults: from immune decline to signal reconstitution strategies
By Shin HS, Lee KS, Park JY et al.
Immunosenescence is characterized by progressive deterioration of innate and adaptive immune function, resulting in reduced vaccine efficacy, durability, and immune quality in older adults. Age-associated alterations include impaired dendritic cell activation, reduced type I interferon production, diminished naïve T-cell output, defective T follicular helper cell differentiation, weakened germinal center responses, and chronic low-grade inflammation. Consequently, vaccine responsiveness in older adults is often limited by defects in immune signaling and coordination that cannot be fully overcome by antigen optimization alone. In this review, we examine the biological basis of immunosenescence and discuss how vaccine adjuvants can improve immune responses in aging populations. We propose a conceptual framework in which adjuvants act through three non-mutually exclusive mechanisms: signal amplification, signal reconstitution, and functional bypass. Using this framework, we evaluate licensed adjuvants currently used in older adults, including AS01, MF59, AS03, and CpG1018, and discuss emerging adjuvant platforms under development. Collectively, current evidence suggests that effective vaccination in older adults requires strategies that address age-associated immune dysfunction in addition to antigen delivery. A better understanding of immunosenescence and adjuvant biology may facilitate the development of precision vaccination approaches tailored to specific immune deficits in aging populations.