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Project description:Seasonal influenza contributes to a substantial disease burden annually, resulting in approximately 10 million hospital visits and 50 thousand deaths in a typical year in the US. 90% of the annual mortality from influenza occurs in people over the age of 65. While influenza vaccination is the best protection against the virus, it is less effective for the elderly. This may be due to differences in the quantity or type of B cells induced by vaccination in older individuals. To investigate this possibility, we leveraged recent development in single-cell technology that allows for simultaneous measurement of both gene expression profile and the B cell receptor (BCR) at single-cell resolution. Pre- and post-vaccination peripheral blood B cells were sorted from three young and three older adults who responded to the inactivated influenza vaccine and were profiled using single-cell RNAseq with paired BCR sequencing. At pre-vaccination, we observed a higher somatic hypermutation frequency and a higher abundance of activated B cells in older adults than in young adults. Following vaccination, young adults mounted a more clonal response than older adults. The response involved a mix of plasmablasts, activated B cells, and resting memory B cells in both age groups. The response in young adults was dominated by expansion in plasmablasts, while the response in older adults also involved activated B cells. We observed a consistent change in gene expression in plasmablasts after vaccination between age groups but not in the activated B cells. These quantitative and qualitative differences in the B cell response may provide insights into the age-related change of influenza vaccination response.
2023-08-20 | GSE175523 | GEO
Project description:Seasonal influenza contributes to a substantial disease burden annually, resulting in approximately 10 million hospital visits and 50 thousand deaths in a typical year in the US. 90% of the annual mortality from influenza occurs in people over the age of 65. While influenza vaccination is the best protection against the virus, it is less effective for the elderly. This may be due to differences in the quantity or type of B cells induced by vaccination in older individuals. To investigate this possibility, we leveraged recent development in single-cell technology that allows for simultaneous measurement of both gene expression profile and the B cell receptor (BCR) at single-cell resolution. Pre- and post-vaccination peripheral blood B cells were sorted from three young and three older adults who responded to the inactivated influenza vaccine and were profiled using single-cell RNAseq with paired BCR sequencing. At pre-vaccination, we observed a higher somatic hypermutation frequency and a higher abundance of activated B cells in older adults than in young adults. Following vaccination, young adults mounted a more clonal response than older adults. The response involved a mix of plasmablasts, activated B cells, and resting memory B cells in both age groups. The response in young adults was dominated by expansion in plasmablasts, while the response in older adults also involved activated B cells. We observed a consistent change in gene expression in plasmablasts after vaccination between age groups but not in the activated B cells. These quantitative and qualitative differences in the B cell response may provide insights into the age-related change of influenza vaccination response.
2023-08-20 | GSE175522 | GEO
Project description:The seasonal influenza vaccine is an important public health tool but is only effective in a subset of individuals. The identification of molecular signatures provides a mechanism to understand the drivers of vaccine-induced immunity. Most previously reported molecular signatures of human influenza vaccination were derived from a single age group or season, ignoring the effects of immunosenescence or vaccine composition. Thus, it remains unclear how immune signatures of vaccine response change with age across multiple seasons. In this study we profile the transcriptional landscape of young and older adults over five consecutive vaccination seasons to identify shared signatures of vaccine response as well as marked seasonal differences. Along with substantial variability in vaccine-induced signatures across seasons, we uncovered a common transcriptional signature 28 days postvaccination in both young and older adults. However, gene expression patterns associated with vaccine-induced Ab responses were distinct in young and older adults; for example, increased expression of killer cell lectin-like receptor B1 (KLRB1; CD161) 28 days postvaccination positively and negatively predicted vaccine-induced Ab responses in young and older adults, respectively. These findings contribute new insights for developing more effective influenza vaccines, particularly in older adults.
| S-EPMC7755271 | biostudies-literature
Project description:Although valuable and effective in decreasing disease burden, influenza vaccination has low rates of efficacy, especially in those at most risk. Studies have shown that acute exercise can improve vaccine responses, most consistently with weaker antigens. Here we examined the effect of resistance exercise on the acute and longer-term responses to influenza vaccination among healthy older adults. Forty-six participants (47.8% male, mean 73.4 ± 6.6 years) were randomised to perform one 45-min moderate-intensity resistance exercise session or sit quietly prior to the receipt of influenza vaccination. Acute exercise reduced vaccine reactions but had no effect on either antibody responses or development of influenza-like symptoms during six months of follow-up. Psychosocial and behavioural characteristics were examined for potential associations with the responses to vaccination. Participants (n = 36) vaccinated in the previous year had higher baseline antibody titres but not follow-up titres nor more frequent experience of influenza-like symptoms over 6 months compared to those unvaccinated in the previous year. These findings provide further support for the ability of acute exercise to reduce vaccine reactions and suggest risk factors for vaccine responses for future exploration. Highlights • Acute exercise reduced influenza vaccine reactions in older adults.• Acute exercise did not change antibody titres.• Psychosocial and behavioural factors had limited association with responses.
| S-EPMC8474530 | biostudies-literature
Project description:Background: Sex differences in immune responses to influenza vaccine may impact efficacy across populations. Methods: In a cohort of 138 older adults (50-74 years old), we measured influenza A/H1N1 antibody titers, B-cell ELISPOT response, PBMC transcriptomics, and PBMC cell compositions at 0, 3, and 28 days post-immunization with the 2010/11 seasonal inactivated influenza vaccine. Results: We identified higher B-cell ELISPOT responses in females than males. Potential mechanisms for sex effects were identified in four gene clusters related to T, NK, and B cells. Mediation analysis indicated that sex-dependent expression in T and NK cell genes can be partially attributed to higher CD4+ T cell and lower NK cell fractions in females. We identified strong sex effects in 135 B cell genes whose expression correlates with ELISPOT measures, and found that cell subset differences did not explain the effect of sex on these genes' expression. Post-vaccination expression of these genes, however, mediated 41% of the sex effect on ELISPOT responses. Conclusions: These results improve our understanding of sexual dimorphism in immunity and influenza vaccine response.
| S-EPMC6400991 | biostudies-literature
Project description: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. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log2 HAI titers, and fold-rise in log2 HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. 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.
2022-02-16 | GSE196793 | GEO
Project description:Influenza is a highly contagious viral respiratory disease that affects millions of people worldwide each year. Annual vaccination is recommended by the World Health Organization to reduce influenza severity and limit transmission through elicitation of antibodies targeting mainly the hemagglutinin glycoprotein of the influenza virus. Antibodies elicited by current seasonal influenza vaccines are predominantly strain-specific. However, continuous antigenic drift by circulating influenza viruses facilitates escape from pre-existing antibodies requiring frequent reformulation of the seasonal influenza vaccine. Traditionally, immunological responses to influenza vaccination have been largely focused on IgG antibodies, with almost complete disregard of other isotypes. In this report, young adults (18-34 years old) and elderly (65-85 years old) subjects were administered the split inactivated influenza vaccine for 3 consecutive seasons and their serological IgA and IgG responses were profiled. Moreover, correlation analysis showed a positive relationship between vaccine-induced IgA antibody titers and traditional immunological endpoints, exposing vaccine-induced IgA antibodies as an important novel immune correlate during influenza vaccination.
| S-EPMC7249748 | biostudies-literature
Project description:The most profound consequences of immune senescence with respect to public health are the increased susceptibility to influenza and loss of efficacy of the current split-virus influenza vaccines in older adults, which are otherwise very effective in younger populations. Influenza infection is associated with high rates of complicated illness including pneumonia, heart attacks and strokes in the 65+ population. Changes in both innate and adaptive immune function not only converge in the reduced response to vaccination and protection against influenza, but present significant challenges to new vaccine development. In older adults, the goal of vaccination is more realistically targeted to providing clinical protection against disease rather sterilizing immunity. Correlates of clinical protection may not be measured using standard techniques such as antibody titres to predict vaccine efficacy. Further, antibody responses to vaccination as a correlate of protection may fail to detect important changes in cellular immunity and enhanced vaccine-mediated protection against influenza illness in older people. This article will discuss the impact of influenza in older adults, immunologic targets for improved efficacy of the vaccines, and alternative correlates of clinical protection against influenza that are needed for more effective translation of novel vaccination strategies to improved protection against influenza in older adults.
| S-EPMC3061971 | biostudies-literature
Project description:Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure.
| S-EPMC5051070 | biostudies-literature
Project description:BackgroundHigh-dose inactivated influenza vaccine (IIV-HD) is an alternative to the standard-dose inactivated influenza vaccine (IIV-SD) in the United States for influenza prevention in older adults. IIV-HD improved efficacy relative to IIV-SD in a randomized controlled trial. Recent observational studies suggest that previous influenza vaccination may influence the immunogenicity and effectiveness of current-season vaccination.MethodsThe original study was a double-blind, randomized trial comparing IIV-HD to IIV-SD in adults aged ?65 years over 2 influenza seasons. A subset of year 1 (Y1) participants reenrolled in year 2 (Y2), receiving vaccine by random assignment in both years. We evaluated the effect of Y1 vaccination on Y2 relative vaccine efficacy (VE), immunogenicity (hemagglutination inhibition [HAI] titers), and safety among reenrolled participants.ResultsOf 14 500 Y1 participants, 7643 reenrolled in Y2. Relative to participants who received IIV-SD both seasons, VE was higher for IIV-HD vaccinees in Y2 (28.3% overall; 25.1% for Y1 IIV-HD, Y2 IIV-HD; and 31.6% for Y1 IIV-SD, Y2 IIV-HD). In multivariate logistic regression models, Y1 vaccine was not a significant modifier of Y2 VE (P= .43), whereas Y2 IIV-HD remained significantly associated with lower influenza risk (P= .043). Compared to administration of IIV-SD in both years, postvaccination HAI titers were significantly higher for patterns that included IIV-HD in Y2. No safety concerns were raised with IIV-HD revaccination.ConclusionsIIV-HD is likely to provide clinical benefit over IIV-SD irrespective of previous-season vaccination with IIV-HD or IIV-SD. IIV-HD consistently improved immune responses, and no safety concerns emerged in the context of IIV-HD revaccination.
| S-EPMC4826458 | biostudies-literature