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Antibody and Local Cytokine Response to Respiratory Syncytial Virus Infection in Community-Dwelling Older Adults.

ABSTRACT: Respiratory syncytial virus (RSV) is increasingly recognized for causing severe morbidity and mortality in older adults, but there are few studies on the RSV-induced immune response in this population. Information on the immunological processes at play during RSV infection in specific risk groups is essential for the rational and targeted design of novel vaccines and therapeutics. Here, we assessed the antibody and local cytokine response to RSV infection in community-dwelling older adults (?60?years of age). During three winters, serum and nasopharyngeal swab samples were collected from study participants during acute respiratory infection and recovery. RSV IgG enzyme-linked immunosorbent assays (ELISA) and virus neutralization assays were performed on serum samples from RSV-infected individuals (n?=?41) and controls (n?=?563 and n?=?197, respectively). Nasal RSV IgA and cytokine concentrations were determined using multiplex immunoassays in a subset of participants. An in vitro model of differentiated primary bronchial epithelial cells was used to assess RSV-induced cytokine responses over time. A statistically significant increase in serum neutralization titers and IgG concentrations was observed in RSV-infected participants compared to controls. During acute RSV infection, a statistically significant local upregulation of beta interferon (IFN-?), IFN-?1, IFN-?, interleukin 1? (IL-1?), tumor necrosis factor alpha (TNF-?), IL-6, IL-10, CXCL8, and CXCL10 was found. IFN-?, IFN-?1, CXCL8, and CXCL10 were also upregulated in the epithelial model upon RSV infection. In conclusion, this study provides novel insights into the basic immune response to RSV infection in an important and understudied risk population, providing leads for future studies that are essential for the prevention and treatment of severe RSV disease in older adults.IMPORTANCE Respiratory syncytial virus (RSV) can cause severe morbidity and mortality in certain risk groups, especially infants and older adults. Currently no (prophylactic) treatment is available, except for a partially effective yet highly expensive monoclonal antibody. RSV therefore remains a major public health concern. To allow targeted development of novel vaccines and therapeutics, it is of great importance to understand the immunological mechanisms that underlie (protection from) severe disease in specific risk populations. Since most RSV-related studies focus on infants, there are only very limited data available concerning the response to RSV in the elderly population. Therefore, in this study, RSV-induced antibody responses and local cytokine secretion were assessed in community-dwelling older adults. These data provide novel insights that will benefit ongoing efforts to design safe and effective prevention and treatment strategies for RSV in an understudied risk group.

SUBMITTER: Yu X

PROVIDER: S-EPMC7471002 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Antibody and Local Cytokine Response to Respiratory Syncytial Virus Infection in Community-Dwelling Older Adults.

Yu Xiao X Lakerveld Anke J AJ Imholz Sandra S Hendriks Marion M Ten Brink Sofie C A SCA Mulder H Lie HL de Haan Karen K Schepp Rutger M RM Luytjes Willem W de Jong Menno D MD van Beek Josine J van Kasteren Puck B PB

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Respiratory syncytial virus (RSV) is increasingly recognized for causing severe morbidity and mortality in older adults, but there are few studies on the RSV-induced immune response in this population. Information on the immunological processes at play during RSV infection in specific risk groups is essential for the rational and targeted design of novel vaccines and therapeutics. Here, we assessed the antibody and local cytokine response to RSV infection in community-dwelling older adults (≥60 ...[more]

PMID: 32878928

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Project description:IntroductionRespiratory syncytial virus (RSV) is an important cause of severe respiratory illness in older adults and adults with respiratory or cardiovascular comorbidities. Published estimates of its incidence and prevalence in adult groups vary widely. This article reviews the potential limitations affecting RSV epidemiology studies and suggests points to consider when evaluating or designing them.MethodsStudies reporting the incidence or prevalence of RSV infection in adults in high-income Western countries from 2000 onwards were identified via a rapid literature review. Author-reported limitations were recorded, together with presence of other potential limitations. Data were synthesized narratively, with a focus on factors affecting incidence estimates for symptomatic infection in older adults.ResultsA total of 71 studies met the inclusion criteria, most in populations with medically attended acute respiratory illness (ARI). Only a minority used case definitions and sampling periods tailored specifically to RSV; many used influenza-based or other criteria that are likely to result in RSV cases being missed. The great majority relied solely on polymerase chain reaction (PCR) testing of upper respiratory tract samples, which is likely to miss RSV cases compared with dual site sampling and/or addition of serology. Other common limitations were studying a single season, which has potential for bias due to seasonal variability; failure to stratify results by age, which underestimates the burden of severe disease in older adults; limited generalizability beyond a limited study setting; and absence of measures of uncertainty in the reporting of results.ConclusionsA significant proportion of studies are likely to underestimate the incidence of RSV infection in older adults, although the effect size is unclear and there is also potential for overestimation. Well-designed studies, together with increased testing for RSV in patients with ARI in clinical practice, are required to accurately capture both the burden of RSV and the potential public health impact of vaccines.

Project description:BackgroundWith the advancing age of the population, and increasing demands on healthcare services, community participation has become an important consideration for healthy ageing. Low levels of community participation have been linked to increased mortality and social isolation. The extent to which community participation has been measured objectively in older adults remains scarce. This study aims to describe where and how older adults participate in the community and determine the feasibility of measurement methods for community participation.MethodsThis observational cross-sectional study obtained data from 46 community dwelling older adults. A combination of Global Positioning Systems (GPS), accelerometry, and self-reported diaries were used over a 7-day monitoring period. Feasibility of methods were determined by calculating the loss of GPS data, questionnaires, and comparison of self-reported locations with GPS co-ordinates. Relationships between community participation, physical activity, social interactions, health related quality of life, sleep quality and loneliness were explored.ResultsOlder adults took a median (IQR) of 15 (9.25-18.75) trips out of home over the 7-day monitoring period, most frequently visiting commercial and recreational locations. In-home activities were mainly sedentary in nature, with out of home activities dependent on location type. Self-reported and GPS measures of trips out of home and the locations visited were significantly correlated (self-report 15.7 (5.6) GPS 14.4 (5.8) (r = 0.94)). Significant correlations between both the number of trips taken from home, with social interactions (r = 0.62) and the minutes of moderate to vigorous physical activity (MVPA) (r = 0.43) were observed. Daily MVPA was higher in participants who visited local walk/greenspaces (r = 0.48).ConclusionParticipants performed more activities with social interactions out of home and visited commercial locations most frequently. The combination of GPS, accelerometry and self-report methods provided a detailed picture of community participation for older adults. Further research is required with older adults of varying health status to generalise the relationships between community participation, location and physical activity.Trial registrationEthical approval was gained from the Flinders University Social and Behavioural Research Ethics Committee (protocol no. 8176).

Project description:Blood-based inflammatory markers hold considerable promise for diagnosis and prognostication of age-related neurodegenerative disease, though a paucity of research has empirically tested how reliably they can be measured across different experimental runs ("batches"). We quantified the interbatch reliability of 13 cytokines and chemokines in a cross-sectional study of 92 community-dwelling older adults (mean age = 74; 48% female). Plasma aliquots from the same blood draw were parallelly processed in 2 separate batches using the same analytic platform and procedures (high-performance electrochemiluminescence by Meso Scale Discovery). Interbatch correlations (Pearson's r) ranged from small and nonsignificant (r = .13 for macrophage inflammatory protein-1 alpha [MIP-1α]) to very large (r > .90 for interferon gamma [IFNγ], interleukin-10 [IL-10], interferon gamma-induced protein 10 [IP-10], MIP-1β, thymus and activation-regulated chemokine [TARC]) with most markers falling somewhere in between (.67 ≤ r ≤ .90 for IL-6, tumor necrosis factor alpha [TNF-α], Eotaxin, Eotaxin-3, monocyte chemoattractant protein-1 [MCP-1], MCP-4, macrophage-derived chemokine [MDC]). All markers, except for IL-6 and MCP-4, showed significant differences in absolute values between batches, with discrepancies ranging in effect size (Cohen's d) from small to moderate (0.2 ≤ |d| ≤ 0.5 for IL-10, IP-10, MDC) to large or very large (0.68 ≤ |d| ≤ 1.5 for IFNγ, TNF-α, Eotaxin, Eotaxin-3, MCP-1, MIP-1α, MIP-1β, TARC). Relatively consistent associations with external variables of interest (age, sex, systolic blood pressure, body mass index, cognition) were observed across batches. Taken together, our results suggest heterogeneity in measurement reliability of blood-based cytokines and chemokines, with some analytes outperforming others. Future work is needed to evaluate the generalizability of these findings while identifying potential sources of batch effect measurement error.

Dataset Information

Antibody and Local Cytokine Response to Respiratory Syncytial Virus Infection in Community-Dwelling Older Adults.

Publications

Antibody and Local Cytokine Response to Respiratory Syncytial Virus Infection in Community-Dwelling Older Adults.

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