Immunosenescence and human vaccine immune responses

Abstract

The age-related dysregulation and decline of the immune system-collectively termed "immunosenescence"-has been generally associated with an increased susceptibility to infectious pathogens and poor vaccine responses in older adults. While numerous studies have reported on the clinical outcomes of infected or vaccinated individuals, our understanding of the mechanisms governing the onset of immunosenescence and its effects on adaptive immunity remains incomplete. Age-dependent differences in T and B lymphocyte populations and functions have been well-defined, yet studies that demonstrate direct associations between immune cell function and clinical outcomes in older individuals are lacking. Despite these knowledge gaps, research has progressed in the development of vaccine and adjuvant formulations tailored for older adults in order to boost protective immunity and overcome immunosenescence. In this review, we will discuss the development of vaccines for older adults in light of our current understanding-or lack thereof-of the aging immune system. We highlight the functional changes that are known to occur in the adaptive immune system with age, followed by a discussion of current, clinically relevant pathogens that disproportionately affect older adults and are the central focus of vaccine research efforts for the aging population. We conclude with an outlook on personalized vaccine development for older adults and areas in need of further study in order to improve our fundamental understanding of adaptive immunosenescence.

Keywords: Adaptive immunity; Aging; B cell; Immune response; Immunosenescence; T cell; Vaccination.

Fig. 1

Immunological changes associated with aging and adaptive immunosenescence. Specific changes in the T and B cell compartments are known to occur with aging and the onset of immunosenescence. Naïve lymphocyte production, lymphocyte repertoire diversity, and the proliferative and functional capacity of effector lymphocytes all decline with age; similarly, increases in differentiated memory cell populations, lymph node fibrosis, and altered cytokine production all occur. These phenomena have been collectively associated with diminished vaccine responses and an increased susceptibility to viral infectious diseases in older adults. The mechanisms by which immunosenescence operates are not fully understood, and systems biology approaches are currently focused on elucidating these mechanisms in order to inform the rational design of vaccines for older adults