Reviews and feature article
Clinical reviews in allergy and immunology
Influence of immune aging on vaccine responses

https://doi.org/10.1016/j.jaci.2020.03.017Get rights and content

Impaired vaccine responses in older individuals are associated with alterations in both the quantity and quality of the T-cell compartment with age. As reviewed herein, the T-cell response to vaccination requires a fine balance between the generation of inflammatory effector T cells versus follicular helper T (TFH) cells that mediate high-affinity antibody production in tandem with the induction of long-lived memory cells for effective recall immunity. During aging, we find that this balance is tipped where T cells favor short-lived effector but not memory or TFH responses. Consistently, vaccine-induced antibodies commonly display a lower protective capacity. Mechanistically, multiple, potentially targetable, changes in T cells have been identified that contribute to these age-related defects, including posttranscription regulation, T-cell receptor signaling, and metabolic function. Although research into the induction of tissue-specific immunity by vaccines and with age is still limited, current mechanistic insights provide a framework for improved design of age-specific vaccination strategies that require further evaluation in a clinical setting.

Key words

Vaccination
antibody
T cells
T-cell receptor
recall response
age

Abbreviations used

ABC
Age-associated B cell
AID
Activation-induced cytidine deaminase
BCR
B-cell receptor
JEV
Japanese encephalitis virus
miR
microRNA
mTORC
mTOR complex
SLT
Secondary lymphoid tissue
TCR
T-cell receptor
TFH
T follicular helper cell
VZV
Varicella zoster virus
YF
Yellow fever

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This work was supported by the National Institutes of Health (grant no. R01 AI108906 to C.M.W., grant nos. R01 AI108891, R01 AG045779, U19 AI057266, and R01 AI129191 to J.J.G., and Irene Diamond/AFAR Postdoctoral Transition Award to C.E.G.) and with resources and the use of facilities at the Palo Alto Veterans Administration Healthcare System. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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