Frailty is associated with impairment of vaccine-induced antibody response and increase in post-vaccination influenza infection in community-dwelling older adults
Introduction
Seasonal influenza causes significant morbidity and mortality in older adults [1], [2], [3]. A large number of studies have shown the efficacy of annual immunization with TIV (Cochrane Database Systemic Review) [4], which is the current vaccination strategy against influenza infection in this population. For example, the efficacy of TIV immunization in relatively young and healthy seniors has been demonstrated by controlled trials [5], [6] and prospective observational studies [7], [8]. Nichol and colleagues have shown the effectiveness of annual TIV immunization in working adults aged 50–64 years as well as in the elderly [9], [10], [11], [12]. However, Simonsen et al. reported that increased vaccination coverage over the past 2 decades failed to reduce influenza-related mortality in older adults [13], [14], [15]. A nested case–control study, with the majority of its study population being over 70 years, demonstrated no significant benefit of TIV immunization against pneumonia secondary to influenza infection [16]. Impaired functional status has also been associated with decreased mortality benefit of TIV immunization in the elderly [17]. These studies suggest significant controversy in the current literature regarding the clinical effectiveness of TIV immunization in this highly heterogeneous population as well as the need for further evaluation of the effectiveness of TIV immunization in subsets of seniors who are older and frail.
Frailty is an important geriatric syndrome characterized by decreased physiologic reserve and increased vulnerability with multi-system dysregulation, leading to hospitalization, dependency, and early mortality in older adults [18], [19], [20], [21]. A 5-item set of criteria has been validated in multiple studies to identify seniors who are frail and vulnerable to adverse health outcomes in the community [18], [21], [22], [23], [24]. Based on these criteria, frailty has an estimated prevalence of 7% among community-dwelling men and women 65 years and older, and up to 30% in those over 80 years [18], [23]. Evidence from our group and others suggests that frail older adults manifest a heightened inflammatory state and significant dysregulation in the innate and T cell compartments that appear to be above and beyond age-related senescent immune remodeling [22], [25], [26], [27], [28], [29], [30], [31]. However, potential impact of frailty on TIV-induced antibody response and its clinical effectiveness in the elderly population has not been adequately investigated.
The objective of this study was to evaluate TIV-induced strain-specific HI antibody titers as well as post-vaccination rates of influenza-like illness (ILI) and laboratory confirmed influenza infections in frail and nonfrail older adults. We hypothesized that frail older persons would have lower HI titers to TIV immunization and higher post-vaccination rates of ILI and laboratory-confirmed influenza infections than nonfrail controls. The results indicate that assessing frailty status in the elderly may identify those who are less likely to respond to TIV immunization and be at higher risk for seasonal influenza and its complications.
Section snippets
Study design and participants
This is a prospective observational study of the potential influence of the frailty syndrome on strain-specific antibody response and clinical effectiveness of influenza immunizations with TIV in older adults. The study was performed during 2007–2008 influenza season. Community-dwelling older adults over 70 were recruited via collaborating physicians and community newspaper advertisement and flyers at outpatient clinics, senior centers, retirement communities, and residential areas in
Characteristics of the study participants
Of 94 persons initially screened, 78 (83%) met the eligibility criteria and enrolled into the study. Seven individuals were lost follow-up due to either moving out of the area for the winter season (n = 4), refusal of providing a post-vaccination blood specimen (n = 2), or being hospitalized after an accidental fall and subsequent death (n = 1). This yielded a final sample size of 71 (91% of the total enrolled). Table 1 summarizes major demographic and clinical characteristics of the study population
Discussion
Here we demonstrate for the first time, the significant impact of the geriatric syndrome of frailty on TIV immunization. Specifically, we have shown that frailty is associated with decreased HI titer response to TIV immunization and increased rates of post-vaccination ILI and influenza infection in community-dwelling older adults. Participants with no ILI had better antibody response to TIV immunization as indicated by significantly higher post-immunization HI titers and most seroconversions
Acknowledgements
Sean Leng is a current recipient of the Paul Beeson Career Development Award in Aging Research, K23 AG028963, (supported by the National Institute on Aging, the American Federation for Aging Research, The John A. Hartford Foundation, The Atlantic Philanthropies, The Starr Foundation and an anonymous donor).
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Post-doctoral fellow from Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.