Frailty is usually accompanied by greater immune dysfunction, given that chronic inflammation is a strong component of both immune aging and the various dysfunctions of frailty. Thus frail individuals exhibit a worse response to vaccinations intended to prevent infectious disease. This is unfortunate, as this is the population in greatest need of the defense of vaccination. This is illustrated every year by the toll of deaths due to influenza, and particularly this year by the ongoing COVID-19 pandemic. A great deal of effort goes into attempts to improve vaccine efficiency in older people, but ultimately that vaccine efficiency is limited in any given individual by the state of the aged immune system. It would be better to put those resources towards the development of the most promising approaches to rejuvenation of immune function: thymic regrowth, restoration of the hematopoietic system, and so forth.
The burden of influenza-related morbidity and mortality among older adults is substantial. Surveillance studies estimate that 71%-85% of influenza deaths occur in adults ≥65 years of age. Adults ≥65 years are 10 to 30 times more likely than younger adults to experience acute respiratory failure attributed to influenza disease. Low vaccine effectiveness among the elderly has been attributed to senescence of the immune system and a decreased immune response to vaccine antigens. Overlaid on age-related immunosenescence are the effects of frailty, a multi-dimensional syndrome marked by losses in function and physiological reserve. Physical frailty is characterized by diminished strength, endurance, and reduced physiologic function.
Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine.
Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.
Link: https://doi.org/10.18632/aging.202207
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