Safe Listeria monocytogenes-based vaccine vector
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ABSTRACT:
PROVIDER: PRJEB43038 | ENA |
REPOSITORIES: ENA
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Project description:Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses, which can augment early immune responses and contribute to protection from lethal infection. Thus, we reasoned MAIT cells may have an adjuvating role in the immunogenicity of replication-incompetent adenovirus vectors, which are novel vaccine platforms for pandemic pathogens such as Ebola virus and SARS-CoV-2. In both mice and human volunteers, immunization with ChAdOx1 (Chimpanzee Adenovirus Ox1) robustly activated MAIT cells. Activation required transduction of plasmacytoid dendritic cells and monocytes to produce IFN- and IL-18, respectively. IFN--induced monocyte-derived TNF was identified as a novel intermediate in this activation pathway, and activation required combinatorial signaling of all three cytokines both in vitro and in vivo. Strikingly, vaccine-induced activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers. Supporting a causal relationship, MAIT cell-deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. These findings define a novel role for MAIT cells in the immunogenicity of adenovirus vector vaccines, with potential implications for vaccine design.
2020-10-01 | GSE158835 | GEO
Project description:Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Climate change is projected to lead to an increase in the burden of vector- and water-borne, as well as zoonotic infectious diseases including COVID-19. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts. We applied cutting edge multi-omics approaches to characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final hepatitis B antibody titres. Using both a molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we overcame the p>>>n problem (predictors much greater than observations) and uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Correlations were identified with signalling pathways such as JAK-STAT and interleukin signalling, Toll-Like Receptor Cascades, interferon signalling and Th17 cell differentiation. This study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.
2020-12-21 | GSE161020 | GEO
Project description:Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Climate change is projected to lead to an increase in the burden of vector- and water-borne, as well as zoonotic infectious diseases including COVID-19. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts. We applied cutting edge multi-omics approaches to characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final hepatitis B antibody titres. Using both a molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we overcame the p>>>n problem and uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Correlations were identified with signalling pathways such as JAK-STAT and interleukin signalling, Toll-Like Receptor Cascades, interferon signalling and Th17 cell differentiation. This study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.
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Project description:To investigate the transcriptional response in whole blood from administration of the Cytomegolovirus vaccine vector against heterologous avian flu
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Project description:Here we conducted a bulk RNA-seq analysis of whole blood samples collected from RMs administered with RhCMV vector vaccines using a prime-boost strategy. Two vaccines were used in this study, including 68-1 RhCMV/TB-6Ag (encoding 6 Mtb protein immunogens) and its attenuated variant, 68-1 RhCMV/Δpp71-TB-6Ag (a cell to cell spread-deficient vaccine vector lacking the Rh110 gene encoding the pp71 tegument protein).
2024-10-04 | GSE273911 | GEO
Project description:Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.
2024-12-01 | GSE269423 | GEO
Project description:Live-attenuated viral vaccines have been successfully used to combat infectious disease for decades but due to their empirical derivation, little is known about their mechanisms of attenuation. This lack of understanding makes the development of next generation live attenuated vaccines difficult. The success of the 17D vaccine and availability of the parent virus, Asibi, makes it an excellent model to understand the molecular basis of attenuation of a live attenuated vaccine and the effects of viral diversity on vaccine function. Due to the differences in genetic diversity between WT Asibi virus and its 17D vaccine derivative, we investigated the changes in genetic diversity of 17D and Asibi viruses following treatment with ribavirin.
2020-01-01 | E-MTAB-8504 | biostudies-arrayexpress
Project description:The impact of global climate change on the transmission dynamics of infectious diseases is the subject of extensive debate. The transmission of mosquito-borne viral diseases is particularly complex, with climatic variables directly affecting many parameters associated with the prevalence of disease vectors. While evidence shows that warmer temperatures often decrease the extrinsic incubation period of an arthropod-borne virus (arbovirus), exposure to cooler temperatures often predisposes disease vector mosquitoes to higher infection rates. RNA interference pathways are essential to antiviral immunity in the mosquito; however, few experiments have explored the effects of temperature on the RNAi machinery.
2013-08-13 | GSE46204 | GEO