The unmet need in the elderly: How immunosenescence, CMV infection, co-morbidities and frailty are a challenge for the development of more effective influenza vaccines

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• 作者：Janet E. McElhaney^a ; ^{janet.mcelhaney@ubc.ca} ; ^{JMCELHANEY@UCHC.EDU} ; Xin Zhou^c ; H. Keipp Talbot^d ; Ernst Soethout^e ; R. Chris Bleackley^f ; David J. Granville^b ; Graham Pawelec^g
• 关键词：Older adults ; Elderly ; Influenza ; Influenza vaccine ; Granzyme B ; Inflammation ; CMV
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：9 March, 2012
• 卷：30
• 期：12
• 页码：2060-2067
• 文件大小：810 K

摘要

Influenza remains the single most important cause of excess disability and mortality during the winter months. In spite of widespread influenza vaccination programs leading to demonstrated cost-savings in the over 65 population, hospitalization and death rates for acute respiratory illnesses continue to rise. As a person ages, increased serum levels of inflammatory cytokines are commonly recorded (TNF-伪, IL-1, IL-6). Termed 鈥渋nflammaging鈥? this has been linked to persistent cytomegalovirus (CMV) infection and immune senescence, while increased anti-inflammatory cytokines (IL-10, TGF-尾) are possibly associated with more healthy aging. Paradoxically, a shift with aging toward an anti-inflammatory (IL-10) response and decline in the IFN-纬:IL-10 ratio in influenza-challenged peripheral blood mononuclear cells is associated with a decline in the cytolytic capacity of CD8+ T cells responsible for clearing influenza virus from infected lung tissue. Thus, it is seemingly counter intuitive that the immune phenotype of healthy aging predicts a poor cell-mediated immune response and more serious outcomes of influenza. Herein we postulate a mechanistic link between the accumulation of late-stage, potentially terminally differentiated T cells, many or most of which result from CMV infection, and the immunopathogenesis of influenza infection, mediated by granzyme B in older adults. Further, adjuvanted influenza vaccines that stimulate inflammatory cytokines and suppress the IL-10 response to influenza challenge, would be expected to enhance protection in the 65+ population.