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Homo sapiens

ABSTRACT: Transcriptional responses to RTS,S standard regimen (RRR) and Ad35.CS+R,R vaccination in controlled human malaria infection study

PROVIDER: PRJNA401870 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5999200_1.fastq.gz	Fastqsanger.gz
	SRR5999200_2.fastq.gz	Fastqsanger.gz
	SRR5999210_1.fastq.gz	Fastqsanger.gz
	SRR5999210_2.fastq.gz	Fastqsanger.gz
	SRR5999220_1.fastq.gz	Fastqsanger.gz

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Transcriptional responses to RTS,S induced vaccination in controlled human malaria infection studies

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Project description:In a phase 3 trial in African infants/children, the RTS,S/AS01 (GSK) vaccine showed moderate efficacy against clinical malaria. We aimed to identify RTS,S/AS01-induced signatures associated with clinical malaria by analyzing antigen-stimulated peripheral blood mononuclear cells sampled from a subset of trial participants at baseline and month 3 (one month post-final dose). RTS,S/AS01 vaccination was associated with downregulation of B-cell and monocyte-related blood transcriptional modules (BTMs) and upregulation of T-cell related BTMs, as well as higher month 3 (vs baseline) (CSP)-specific CD4+ T-cell responses. For some RTS,S/AS01-associated BTMs, month 3 levels correlated with anti-circumsporozoite protein (CSP) IgM and inversely with anti-CSP IgG responses. There were few RTS,S/AS01-associated BTMs whose month 3 levels correlated with malaria risk. In contrast, baseline levels of dendritic cell and monocyte RTS,S/AS01-associated BTMs correlated with malaria risk. A cross-study analysis supported generalizability of these correlations to healthy, malaria-naïve adults, suggesting inflammatory monocytes may inhibit protective RTS,S/AS01-induced responses.

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