Sex Differences in Older Adults' Immune Responses to Seasonal Influenza Vaccination.
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ABSTRACT:
SUBMITTER: Voigt EA
PROVIDER: S-EPMC6400991 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PBMC transcriptomes after influenza vaccination contain valuable information about factors affecting vaccine responses. However, distilling meaningful knowledge out of these complex datasets is often difficult and requires advanced data mining algorithms. We investigated the use of the data-driven Weighted Gene Correlation Network Analysis (WGCNA) gene clustering method to identify vaccine response-related genes in PBMC transcriptomic datasets collected from 138 healthy older adults (ages 50-74) before and after 2010-2011 seasonal trivalent influenza vaccination. WGCNA separated the 14,197 gene dataset into 15 gene clusters based on observed gene expression patterns across subjects. Eight clusters were strongly enriched for genes involved in specific immune cell types and processes, including B cells, T cells, monocytes, platelets, NK cells, cytotoxic T cells, and antiviral signaling. Examination of gene cluster membership identified signatures of cellular and humoral responses to seasonal influenza vaccination, as well as pre-existing cellular immunity. The results of this study illustrate the utility of this publically available analysis methodology and highlight genes previously associated with influenza vaccine responses (e.g., CAMK4, CD19), genes with functions not previously identified in vaccine responses (e.g., SPON2, MATK, CST7), and previously uncharacterized genes (e.g. CORO1C, C8orf83) likely related to influenza vaccine-induced immunity due to their expression patterns.
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Project description:Older adults (≥65 years of age) bear a significant burden of severe disease and mortality associated with influenza, despite relatively high annual vaccination coverage and substantial pre-existing immunity to influenza. To test the hypothesis that host factors, including age and sex, play a role in determining the effect of repeated vaccination and levels of pre-existing humoral immunity to influenza, we evaluated pre- and post-vaccination strain-specific hemagglutination inhibition (HAI) titers in adults over 75 years of age who received a high-dose influenza vaccine in at least four out of six influenza seasons. Pre-vaccination titers, rather than host factors and repeated vaccination were significantly associated with post-vaccination HAI titer outcomes, and displayed an age-by-sex interaction. Pre-vaccination titers to H1N1 remained constant with age. Titers to H3N2 and influenza B viruses decreased substantially with age in males, whereas titers in females remained constant with age. Our findings highlight the importance of pre-existing immunity in this highly vaccinated older adult population and suggest that older males are particularly vulnerable to reduced pre-existing humoral immunity to influenza.
| S-EPMC8660902 | biostudies-literature
Project description:Seasonal influenza vaccination has different implications on the immune response depending on the comorbidities. Diabetes is one such critical disease that increases the patient's susceptibility to influenza and suppresses vaccine efficacy and immunity. The sex of the individuals also plays a definitive role in the immune responses to both the vaccine and the infection. This study aims to understand the efficacy of the seasonal vaccine against influenza in diabetic groups and undergoing immune mechanisms in different sexes (females and males). In this study, we are reporting about a switching of the immune response of the infected and vaccinated diabetic females towards stronger Th1/Th17 responses with suppressed humoral immunity. They show increased cDC1, enhanced proinflammatory activities within T cells, CD8T activation, Th17 proliferation, and the majority of IgG2 antibody subtypes with reduced neutralization potential. Males with diabetes exhibit enhanced humoral Th2-immunity than the nondiabetic group. They exhibit higher cDC2, and DEC205 levels within them with an increase in plasma B lymphocytes, higher IgG1 subtypes in plasma cells, and influenza-hemagglutinin-specific IgG titer with stronger virus neutralization potential. Males with diabetes recovered better than the females as observed from the changes in their body weight. This study highlights the critical immune mechanisms and sex-specific swapping of their preferred immune response pathways against influenza after vaccination during diabetes. We propose a need for a sex-specific customized vaccine regimen to be implemented against influenza for individuals having diabetes to exploit the manifested strength and weakness in their protective immunity.
| S-EPMC10597737 | biostudies-literature
Project description:Annual vaccination against seasonal influenza is recommended to decrease disease-related mortality and morbidity. However, one population that responds suboptimally to influenza vaccine is adults over the age of 65 years. The natural aging process is associated with a complex deterioration of multiple components of the host immune system. Research into this phenomenon, known as immunosenescence, has shown that aging alters both the innate and adaptive branches of the immune system. The intricate mechanisms involved in immune response to influenza vaccine, and how these responses are altered with age, have led us to adopt a more encompassing systems biology approach to understand exactly why the response to vaccination diminishes with age. Here, the authors review what changes occur with immunosenescence, and some immunogenetic factors that influence response, and outline the systems biology approach to understand the immune response to seasonal influenza vaccination in older adults.
| S-EPMC3514506 | biostudies-literature
Project description:In advance of a large influenza vaccine effectiveness (VE) cohort study among older adults in Thailand, we conducted a population-based, cross-sectional survey to measure vaccine coverage and identify factors associated with influenza vaccination among older Thai adults that could bias measures of vaccine effectiveness.We selected adults ?65 years using a two-stage, stratified, cluster sampling design. Functional status was assessed using the 10-point Vulnerable Elders Survey (VES); scores ?3 indicated vulnerability. Questions about attitudes towards vaccination were based on the Health Belief Model. The distance between participants' households and the nearest vaccination clinic was calculated. Vaccination status was determined using national influenza vaccination registry. Prevalence ratios (PR) and 95% confidence intervals (CIs) were calculated using log-binomial multivariable models accounting for the sampling design.We enrolled 581 participants, of whom 60% were female, median age was 72 years, 41% had at least one chronic underlying illness, 24% met the criteria for vulnerable, and 23% did not leave the house on a daily basis. Influenza vaccination rate was 34%. In multivariable models, no variable related to functional status was associated with vaccination. The strongest predictors of vaccination were distance to the nearest vaccination center (PR 3.0, 95% CI 1.7-5.1 for participants in the closest quartile compared to the furthest), and high levels of a perception of benefits of influenza vaccination (PR 2.8, 95% CI 1.4-5.6) and cues to action (PR 2.7, 95% CI 1.5-5.1).Distance to vaccination clinics should be considered in analyses of influenza VE studies in Thailand. Strategies that emphasize benefits of vaccination and encourage physicians to recommend annual influenza vaccination could improve influenza vaccine uptake among older Thai adults. Outreach to more distant and less mobile older adults may also be required to improve influenza vaccination coverage.
| S-EPMC5706686 | biostudies-literature
Project description:BackgroundWomen/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to generate hypotheses as to the biological mechanism underpinning the AE reported.ResultsA total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference.ConclusionsThese data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.
| S-EPMC10463383 | biostudies-literature
Project description:Background Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to elucidate a possible biological mechanism for the AE reported. Results A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. Conclusions These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.
| S-EPMC9934749 | biostudies-literature
Project description:Epidemiological data suggest that influenza vaccination protects against all-cause mortality in chronic obstructive pulmonary disease (COPD) patients. However, recent work has suggested there is a defect in the ability of some COPD patients to mount an adequate humoral response to influenza vaccination. The aim of our study was to investigate humoral and cell-mediated vaccine responses to the seasonal trivalent influenza vaccination (TIV) in COPD subjects and healthy controls. Forty-seven subjects were enrolled into the study; 23 COPD patients, 13 age-matched healthy controls (HC ≥ 50) and 11 young healthy control subjects (YC ≤ 40). Serum and peripheral blood mononuclear cells (PBMC) were isolated pre-TIV vaccination and at days 7 and 28 and 6 months post-vaccine for haemagglutinin inhibition (HAI) titre, antigen-specific T cell and antibody-secreting cell analysis. The kinetics of the vaccine response were similar between YC, HC and COPD patients and there was no significant difference in antibody titres between these groups at 28 days post-vaccine. As we observed no disease-dependent differences in either humoral or cellular responses, we investigated if there was any association of these measures with age. H1N1 (r = -0·4253, P = 0·0036) and influenza B (r = -0·344, P = 0·0192) antibody titre at 28 days negatively correlated with age, as did H1N1-specific CD4+ T helper cells (r = -0·4276, P = 0·0034). These results suggest that age is the primary determinant of response to trivalent vaccine and that COPD is not a driver of deficient responses per se. These data support the continued use of the yearly trivalent vaccine as an adjunct to COPD disease management.
| S-EPMC6718283 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-08-20 | GSE175524 | GEO
Project description:Clinical data showed sex variability in the immune response to influenza vaccination, this study aimed to investigate differentially expressed genes that contribute to sex-bias immune responses to quadrivalent inactivated influenza vaccines (QIVs) in older subjects. A cohort of 60 healthy older adults aged 60 to 80 years old were vaccinated with quadrivalent inactivated influenza vaccines (QIVs), and gene expression was analyzed at Day 0 pre-vaccination, Day 3, Day 28 and Day 180 post-vaccination. Sexual dimorphism of humoral immunity was analyzed by HAI assay, and the correlation of gene expression patterns of two sex groups with humoral immune response to vaccination was analyzed. The differentially expressed genes involved in type I interferon signaling pathway and complement activation of classical pathway were upregulated within 3 days post-vaccination in females. At Day 28 after immunization, the immune response showed a man-bias pattern associated with the regulation of protein processing and complement activation of classical pathway. A list of differentially expressed genes associated with variant responses to influenza vaccination between women and men were identified by biology-driven clustering. Old women have a greater immune response to QIVs but rapid decline of antibody levels, while old men have the advantages to sustain a durable response to influenza vaccination. In addition, we identified genes that may contribute to the sex variations toward influenza vaccination in the aged. Our findings highlight the importance of developing personalized seasonal influenza vaccines.
2020-11-09 | GSE151558 | GEO