Interferon and inflammasome networks are associated with lower neutralizing antibody responses to Yellow Fever vaccination
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PROVIDER: PRJNA517957 | ENA |
REPOSITORIES: ENA
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Project description:The immune response to vaccines is critically dependent on multiple host and environmental factors including acute and chronic infections as well as metabolic and/or pathophysiological states of the host. In this study, we used computational systems biology to analyze a cohort of Ugandan subjects following immunization with the Yellow Fever vaccine (YF-17D) to identify pre-vaccination molecular and cellular mechanisms that are associated with the response to the vaccine. By integrating gene expression profiling, cell subset phenotyping and cytokine measurements, we highlight the upregulated levels of interferon-regulated, and inflammasome genes and proteins at the time of vaccination as negative correlates of the antibody response to the YF-17D vaccine. We show that this innate immune response is associated with higher levels of genes that interact with bacterial components and with increased frequencies of Tr1 CD39+ IL-10 producing cells. Our results provide a framework to define the influence of environmental parameters present prior to vaccination on the response to vaccines in human populations
2019-01-31 | GSE125921 | GEO
Project description:Mechanisms of poor responses to vaccines remain unknown. Yellow fever-naïve adults were vaccinated with a yellow fever vaccine (YF-17D, Stamaril). Transcriptomic profilling of blood collected pre-vaccination and post-vaccination (day 3, 7, 14 and 84) was performed in order to identify candidate biomarkers of antibody response to the vaccine.
2020-05-19 | GSE136163 | GEO
Project description:The non-human primate (NHP) model (specifically rhesus and cynomolgus macaques) has facilitated our understanding of the pathogenic mechanisms of yellow fever (YF) disease and allowed evaluation of safety and efficacy of YF-17D vaccines. However, the accuracy of this model in mimicking vaccine-induced immunity in humans remains to be fully determined. We used a system biology approach to compare hematological, biochemical, transcriptomic, innate and antibody-mediated immune responses in cynomolgus macaques and human participants following YF-17D vaccination. Immune response progression in cynomolgus macaques followed a similar course as in adult humans, but with slightly earlier onset. Yellow fever virus neutralizing antibody responses occurred earlier in cynomolgus macaques (by Day 7 [D7]), but titers >10 were reached in both species by D14 post-vaccination and were not significantly different by D28 (PRNT50 titers 3.6 Log vs 3.5 Log in cynomolgus macaques and human participants, respectively; p = 0.821). Changes in neutrophils, NK cells, monocytes, T and B cell frequency were higher in cynomolgus macaques and persisted for four weeks versus less than two weeks in humans. Low levels of systemic inflammatory cytokines (IL-1Ra, IL-8, MIP-1α, IP-10, MCP-1 or VEGF) were detected in either or both species, but with no or only slight changes versus baseline. Similar changes in gene expression profiles were elicited in both species. These included enriched and up-regulated type I IFN-associated viral sensing, antiviral innate response, and dendritic cell activation pathways D3–D7 post-vaccination in both species. Hematological and blood biochemical parameters remained relatively unchanged versus baseline in both species. Low level YF-17D viremia (RNAemia) was transiently detected in some cynomolgus macaques (28% [5/18]) but generally absent in humans (except one participant [5%; 1/20]). Importance: Cynomolgus macaques were confirmed as a valid surrogate model for replicating YF-17D vaccine-induced responses in humans, and suggest a key role for type I IFN.
2024-03-29 | GSE253538 | GEO
Project description:Correlates of immune mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of forty volunteers followed for up to one year after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity including complement, the inflammasome and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (Modular IMmune In vitro Construct (MIMIC) system), by the coordinated up-regulation of transcripts for specific transcription factors including STAT1, IRF7 and ETS2 that are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of masters transcription factors, that lead to the development of a broad, polyfunctional and persistent immune response that integrates all effector cells of the immune system.
2008-12-01 | GSE13699 | GEO
Project description:To better understand how innate immunity to vaccination can lead to lasting protective immunity, we have used systemic bioinformatics approaches to define the signature of the yellow fever specific immune response in a cohort of 21 volunteers.
2017-06-25 | GSE82152 | GEO
Project description:Transcriptional profiling of YF-naïve participants after vaccination against yellow fever.
| PRJNA561414 | ENA
Project description:CHIKV VLP Vaccination in Humans induced broadly neutralizing antibodies
| PRJNA905836 | ENA
Project description:Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo hemorrhagic fever virus (CCHFV), is on the World Health Organizations list over emerging pathogens and prioritized diseases. With global distribution, high fatality rate and no approved treatment or vaccine, CCHF constitute a treat against the global health. In the current study we show full protection of mice against lethal CCHFV infection due to mRNA-LNP vaccination. IFNAR-/- mice received two immunizations with either mRNA-LNP encoding for the CCHFV nucleoprotein, glycoproteins or a combination of both. While unvaccinated mice showed clear signs of severe disease, vaccinated mice was significantly protected. Vaccine induced immune responses due to vaccination was evaluated both in IFNAR-/- and immunocompetent mice and a strong humoral and cellular immune response was observed in both mouse models with high titers of neutralizing antibodies and primed T-cells. In addition, we conducted a proteomic analysis on liver samples from vaccinated and unvaccinated mice after CCHFV infection to determine the effect of vaccination on the protein profile. Similar to what has been observed in humans due to vaccination, there was an effect on metabolic pathways. In conclusion, this study shows very promising results regarding development of a vaccine against CCHFV.
2021-11-15 | PXD023300 | Pride
Project description:IntroductionPrompted by recent amendments of Yellow Fever (YF) vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as a proxy for potentially longer lasting immunity.Methods and findingsPBMCs and serum were collected in six individuals on days 0, 3, 5, 12, 28 and 180, and in 99 individuals >10 years after YF-vaccination. Phenotypic characteristics of YF- tetramer+ CD8+ T-cells were determined using class I tetramers. Antibody responses were measured using a standardized plaque reduction neutralization test (PRNT). Also, characteristics of YF-tetramer positive CD8+ T-cells were compared between individuals who had received a primary- and a booster vaccination. YF-tetramer+ CD8+ T-cells were detectable on day 12 (median tetramer+ cells as percentage of CD8+ T-cells 0.2%, range 0.07-3.1%). On day 180, these cells were still present (median 0.06%, range 0.02-0.78%). The phenotype of YF-tetramer positive CD8+ T-cells shifted from acute phase effector cells on day 12, to late differentiated or effector memory phenotype (CD45RA-/+CD27-) on day 28. Two subsets of YF-tetramer positive T-cells (CD45RA+CD27- and CD45RA+CD27+) persisted until day 180. Within all phenotypic subsets, the T-bet: Eomes ratio tended to be high on day 28 after vaccination and shifted towards predominant Eomes expression on day 180 (median 6.0 (day 28) vs. 2.2 (day 180) p = 0.0625), suggestive of imprinting compatible with long-lived memory properties. YF-tetramer positive CD8+ T-cells were detectable up to 18 years post vaccination, YF-specific antibodies were detectable up to 40 years after single vaccination. Booster vaccination did not increase titers of YF-specific antibodies (mean 12.5 vs. 13.1, p = 0.583), nor induce frequencies or alter phenotypes of YF-tetramer+ CD8+ T-cells.ConclusionThe presence of a functionally competent YF-specific memory T-cell pool 18 years and sufficient titers of neutralizing antibodies 35-40 years after first vaccination suggest that single vaccination may be sufficient to provide long-term immunity.
| S-EPMC4792480 | biostudies-literature