Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans

Epps, Puja Van; Tumpey, Terrence M.; Pearce, Melissa B.; Golding, Hana; Higgins, Patricia A.; Hornick, Thomas; Burant, Christopher J.; Wilson, Brigid; Banks, Richard; Gravenstein, Stefan; Canaday, David H.

doi:10.1128/cvi.00498-16

Cited by 28 publications

(30 citation statements)

References 37 publications

(41 reference statements)

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Section: Discussionsupporting

confidence: 85%

“…The results of the present study are in agreement with other recent reports demonstrating a lack of association between frailty and vaccine-induced humoral responses ( 11 , 12 , 14 , 15 ), while differing from some of the earlier studies where frailty was associated with lower seroconversion rates ( 8 – 10 ). Of note, the recent studies have suggested that the vaccine-induced antibody production is more strongly correlated with pre-existing antibody levels than with frailty stratification ( 14 , 35 ). In this study, both pre-existing HAI titers and post-vaccination seroconversion rates were observed to be similar across frailty groups and a positive correlation between pre-existing and post-vaccination antibody titers was seen similarly to other studies ( 14 , 36 ) confirming that the antibody responses were largely determined by pre-existing antibodies and to a much lesser extent by frailty or age.…”

Section: Discussionsupporting

confidence: 85%

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Influenza Vaccine-Induced Antibody Responses Are Not Impaired by Frailty in the Community-Dwelling Elderly With Natural Influenza Exposure

Narang

Tan

et al. 2018

Front. Immunol.

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Background: Elderly adults over 65 years of age are recommended to receive seasonal influenza vaccination as they are at a higher risk of infection and its complications than the younger community. The elderly are often stratified according to frailty status where frail individuals are more susceptible to adverse health outcomes than their non-frail counterparts, however, it is not known whether immunity induced by influenza vaccination is impaired in the frail elderly.Study Design: Two hundred and five elderly subjects of Chinese ethnicity in Singapore (mean age 73.3 ± 5.3 years, 128 females and 77 males) were administered the recommended trivalent inactivated 2013–14 seasonal influenza vaccine (Vaxigrip™) containing A/H1N1, A/H3N2, and B strains. The elderly subjects were stratified into three groups according to Fried's frailty criteria (59 frail, 85 pre-frail, 61 robust) and were also ranked by Rockwood's frailty index (RFI). Statistical associations were evaluated between frailty status and pre- and post-vaccination antibody titres in sera measured by Hemagglutination inhibition (HAI) and microneutralization (MN) assays. Immunological responses across frailty strata were also studied in terms of leukocyte cellular distribution, cytokine levels and gene expression.Results: Post-vaccination, 83.4% of the subjects seroconverted for A/H1N1, 80.5% for A/H3N2, and 81% for the B strain. The seroconversion rates were comparable across frailty groups (A/H1N1, ANOVA, p = 0.7910; A/H3N2, ANOVA, p = 0.8356, B, ANOVA, p = 0.9741). Geometric mean titres of HAI and MN as well as seroprotection rates were also similar in all three frailty groups and uncorrelated with RFI (Spearman, r = 0.023, p = 0.738). No statistically significant differences were observed between the frailty groups in vaccine-induced modulation of leukocyte populations, cytokine responses, and gene expression profiles of peripheral blood mononuclear cells (PBMCs). Whereas, post- and pre-vaccination HAI titres were positively correlated after adjusting for age and gender (A/H1N1, R2 = 0.216, p = 9.1e−11; A/H3N2, R2 = 0.166, p = 3.4e−8; B, R2 = 0.104, p = 3.1e−5). With most subjects lacking previous history of influenza vaccination, the pre-vaccination titres were likely due to natural exposure and seen to match the pattern of influenza subtype prevalence in the time period of vaccination.Conclusion: The majority of the elderly subjects seroconverted for seasonal influenza upon vaccination, and importantly, influenza vaccination-induced humoral immune responses and seroprotection were similar across the frailty strata, indicating that frail individuals may also benefit from influenza vaccination. Pre-existing antibodies due to natural exposure appeared to positively influence vaccine-induced antibody responses.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 85%

Influenza Vaccine-Induced Antibody Responses Are Not Impaired by Frailty in the Community-Dwelling Elderly With Natural Influenza Exposure

Narang

Tan

et al. 2018

Front. Immunol.

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“…A systematic review of high-dose relative to standard-dose influenza vaccine trials, showed that the better antibody responses to high-dose influenza vaccine was independent of sex, age > 75 years old, frailty, and chronic conditions [52]. This is supported by individual studies from Singapore [53], Germany [49], and the U.S. [54], all of which reported that frailty did not have a significant effect on antibody titres following standard dose vaccination in adults 60 and over. Another study originating from the U.S. found the opposite, where antibody responses were significantly impaired in adults that were frail [55].…”

Section: Impact Of Frailty On Outcomes Of Influenzamentioning

confidence: 94%

The immune response to influenza in older humans: beyond immune senescence

et al. 2020

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Despite widespread influenza vaccination programs, influenza remains a major cause of morbidity and mortality in older adults. Age-related changes in multiple aspects of the adaptive immune response to influenza have been well-documented including a decline in antibody responses to influenza vaccination and changes in the cellmediated response associated with immune senescence. This review will focus on T cell responses to influenza and influenza vaccination in older adults, and how increasing frailty or coexistence of multiple (≥2) chronic conditions contributes to the loss of vaccine effectiveness for the prevention of hospitalization. Further, dysregulation of the production of pro-and anti-inflammatory mediators contributes to a decline in the generation of an effective CD8 T cell response needed to clear influenza virus from the lungs. Current influenza vaccines provide only a weak stimulus to this arm of the adaptive immune response and rely on re-stimulation of CD8 T cell memory related to prior exposure to influenza virus. Efforts to improve vaccine effectiveness in older adults will be fruitless until CD8 responses take center stage.

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“…11 The other found no difference in post-vaccination geometric mean titer ratios between frail and non-frail groups of veterans aged 62 years (mean age D 81 years). 12 To our knowledge, similar studies of adults younger than 65 years of age have not been conducted. The purpose of this study was to examine the effect of physical frailty on immune response to influenza vaccine in community-dwelling adults 50 years of age and determine if those responses differed by age.…”

Section: Introductionmentioning

confidence: 93%

The effect of frailty on HAI response to influenza vaccine among community-dwelling adults ≥ 50 years of age

Moehling

Nowalk

Lin

et al. 2017

Human Vaccines & Immunotherapeutics

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The immune response to vaccine antigens is less robust in older adults because of changes in the aging immune system. Frailty, the multi-dimensional syndrome marked by losses in function and physiological reserve, is increasingly prevalent with advancing age. Frailty accelerates this immunosenescence but the consequence of frailty on immune response specific to influenza vaccine among older adults, is mixed. An observational, prospective study of 114 adults was conducted in the fall of 2013 to assess the association of physical frailty with immune response to standard dose influenza vaccine in community-dwelling adults ≥ 50 years of age. Participants were stratified by age (<65 years and ≥65 years), and vaccine strain (Influenza A/H1N1, A/H3N2 and B) was analyzed separately adjusting for body mass index (BMI) and baseline log hemagglutination inhibition (HAI) titers. Overall, immune responses were lower among those ≥65 years of age than those <65 years. Among those ≥65 years there were no significant differences between frail and non-frail individuals in seroprotection or seroconversion for any influenza strain. Frail individuals <65 years of age compared with non-frail individuals were more likely to be seroprotected and to seroconvert post vaccination. Linear regression models show the same pattern of significant differences between frail and non-frail for those <65 years but no significant differences between frailty groups for those ≥65 years. Additional research may elucidate the reasons for the differences observed between younger frail and non-frail adults.

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Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans

Cited by 28 publications

References 37 publications

Influenza Vaccine-Induced Antibody Responses Are Not Impaired by Frailty in the Community-Dwelling Elderly With Natural Influenza Exposure

Influenza Vaccine-Induced Antibody Responses Are Not Impaired by Frailty in the Community-Dwelling Elderly With Natural Influenza Exposure

The immune response to influenza in older humans: beyond immune senescence

The effect of frailty on HAI response to influenza vaccine among community-dwelling adults ≥ 50 years of age

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