Transcriptional profiling of YF-naïve participants after vaccination against yellow fever.
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PROVIDER: PRJNA561414 | ENA |
REPOSITORIES: ENA
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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.
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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
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Project description:Yellow fever (YF) is a life-threatening mosquito-borne disease prevalent in South America and Africa, accounting for up to 60,000 annual deaths. Between December 2016 and May 2018, Brazil reported its worst YF outbreak this century with a fatality rate of 33.6%. While YF vaccines have shown protective capabilities, the genetic profile of those infected with the wild-type YF virus (YFV) remains uncharacterized. Building on recent findings by Kallas et al. (2019), which discerned clinical and immunological determinants of YF mortality, we conducted a comprehensive transcriptional profiling of blood samples from YFV-infected patients. Our investigation integrated omics data with clinical and immunological metrics, contrasting the wild-type YFV acute infection signature against the response triggered by the YF17D vaccine strain and the signature linked to severe COVID-19. Our analyses revealed key molecular mechanisms of YFV infection and determinants of disease severity. Notably, a comparative assessment elucidated distinct gene expression patterns between wild-type YFV infections, YF17D vaccination, and severe COVID-19. This study offers pivotal insights into the molecular underpinnings of YFV infection and its severity, potentially enhancing our comprehension of viral infections at large.
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Project description:Human Naïve-like CD8 T cells induced by the Yellow Fever Vaccine 17D were compared to the conventional subsets in total CD8 T cells Samples originate from peripheral blood mononuclear cells (PBMC) from 8 different donors vaccinated with the YF-17D vaccine
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Project description:Human Naïve-like CD8 T cells induced by the Yellow Fever Vaccine 17D were compared to the conventional subsets in total CD8 T cells Samples originate from peripheral blood mononuclear cells (PBMC) from 8 different donors vaccinated with the YF-17D vaccine 1'000 cells from various CD8 T cells subsets were purified by flow cytometry, from 8 vaccinees (donors d1 to d8); the subsets (cell types) include: A2/NS4b tetramer positive CCR7+ CD45RA+ CD8 T cells (A2_NS4b Naïve-like), Total Naive (CCR7+ CD45RA+), Total Tscm (CCR7+ CD45RA+ CD58+ CD95+), Total CM (CCR7+ CD45RA-) and Total Effectors (CCR7 negative).
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