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Early spatiotemporal evolution of the immune response elicited by adenovirus vector vaccination

ABSTRACT: Early spatiotemporal evolution of the immune response elicited by adenovirus vector vaccination

PROVIDER: PRJNA1102021 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28740200.fastq.gz	Fastqsanger.gz
	SRR28740300.fastq.gz	Fastqsanger.gz
	SRR28740201.fastq.gz	Fastqsanger.gz
	SRR28740301.fastq.gz	Fastqsanger.gz
	SRR28740202.fastq.gz	Fastqsanger.gz

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Early spatiotemporal evolution of the immune response elicited by adenovirus vector vaccination

Project description:As the first responders to immunological challenges, the innate immune system has the potential to shape and regulate the ensuing adaptive immune response. Many clinical studies evaluating the role of various innate populations in initiating vaccine-elicited immunity have been largely relegated to blood. It is also largely unknown how the immune response to vaccination is initiating and evolving at the earliest time points post-vaccination. We sought to investigate the spatiotemporal evolution of the earliest immune responses to intramuscular adenovirus serotype 26 (Ad26) vector vaccination in blood and tissues. Using transcriptomic profiling, we show that Ad26 vector vaccination elicits broad transcriptomic changes as early as 1 hour post-vaccination across blood and tissues marked by IL-1, TNF-α, and IL-6 pro-inflammatory pathways. Immunologic data reveals an influx of Ly6C+ myeloid cells into muscle by 1 hour post-vaccination. A Ly6C+CD64+ population emerges in muscle and subsequently in the draining lymph node, suggesting that myeloid cells may be significant drivers of vaccine-elicited immune responses following intramuscular vaccination. Moreover, levels of IL-6, MIG, MIP-1α, and MIP-1β measured in serum at 6 hours post-vaccination positively correlated with the frequency of vaccine-elicited CD8+ T cell responses evaluated at 60 days post-vaccination. Taken together, our data suggests that the immune response to Ad26 vector vaccination commences by 1 hour across compartments and that events at as early as 6 hours post-vaccination can shape vaccine-elicited CD8+ T cell responses at memory time points.

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Whole blood RNAseq of SIVmac239-infected Mamu-B*08+/- indian rhesus macaques with and without heterologous adenovirus-vector SIV vaccination

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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.

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Project description:Following exposure to vaccines, antigen-specific CD8+ T-cell responses develop as long-term memory pools. Novel vaccine strategies based on adenoviral vectors, e.g. those developed for HCV, are able to induce and sustain substantial CD8+ T-cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T-cell memory pools induced by an adenoviral vector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include up-regulation of homing receptors, and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet (TBX21). In humans, a novel adenovirus vaccine induced similar CMV-like phenotypes and underlying transcription factor regulation. These data clarify the core features of CD8+ T-cell memory following vaccination with adenovirus vectors and indicate a conserved pathway for memory development shared with persistent herpesviruses.

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MAIT cell activation augments adenovirus vector vaccine immunogenicity

Project description:MAIT cell activation augments adenovirus vector vaccine immunogenicity

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Adenoviral vector vaccination induces a conserved program of CD8+ T cell memory differentiation in mouse and man

2015-09-23 | E-GEOD-73314 | biostudies-arrayexpress

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Project description:Gene expression analysis in lymph nodes and site of injection (intradermal) after vaccination with adenovirus (Ad), modified vaccinia Ankara (MVA) or a mixed formulation of Ad+MVA. The hypothesis tested in the present study was that co-administration of two viral vectors induce a differential gene expression in the site of vaccination (dermis) and the draining lymph nodes that ultimately influences the protective ability of a vaccine against pre-erythrocytic malaria. Total RNA was isolated from the vaccination site (dermis) and lymph nodes after vaccination with adenovirus, MVA or Ad+MVA mixed co-administration after 6h and 24h (ear biopsies) and 9h, 24h and 72h for lymph nodes. Differential gene expression was assessed between vaccinated and non-immunized mice. Four ear biopsy samples did not pass quality control, and are not included in this submission.

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