Aging and vaccines: impact of immunosenescence and inflammaging in vaccine response

Historically, effective vaccination has saved millions of lives and made an enormous contribution to addressing global public health threats. However, aging is an inevitable factor that negatively affects vaccine effectiveness and efficacy. With age, humans develop dysregulation of innate immune pathways, increased levels of proinflammatory markers, thymic involution, declines in T- and B-cell numbers and function, dysregulated metabolism, and epigenetic alterations. Immunosenescence, the gradual deterioration of host immunity with age, plays a critical role in susceptibility to infection, disease progression, and vaccine efficacy. Immunosenescence is often accompanied by inflammaging, an age-related increase in proinflammatory cytokine and chemokine levels. This multifactorial and dynamic process can lead to poor vaccine responses, potentially resulting in higher morbidity and mortality in older adults. Therefore, research focused on understanding the impact of immunosenescence and inflammaging on vaccine response will undoubtedly help optimize vaccine delivery among elderly individuals. In this review, we summarize the most recent knowledge on the multifactorial effects of age-induced immunosenescence and inflammaging and their role in vaccine efficacy against respiratory tract infections. The review further discusses strategic approaches such as IL-7 therapy, senolytic therapy, increasing telomerase activity, use of mTOR inhibitors, B cell therapy, development of broader vaccines and new adjuvants, and positive lifestyle changes, to enhance vaccine immunogenicity and efficacy in older adults. This could provide theoretical insights to improve vaccine effectiveness in the elderly and help address major global health issues.