Plasmodium falciparum
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA235895 | ENA |
REPOSITORIES: ENA
Similar Datasets
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.
2021-06-05 | GSE176156 | GEO
Project description:The goal of this phase 1/2a sporozoite challenge trial (NCT01883609) was to evaluate novel malaria vaccination regimens of the GSK pre-erythrocytic RTS,S/AS01B vaccine alone and concomitantly same-site administered with the viral vectors ChAd63 & MVA encoding the liver stage antigen construct ME-TRAP. Four vaccine groups were studied and received three vaccinations at a monthly interval. All subjects then underwent controlled human malaria infection (CHMI) 11 weeks after first vaccine administration.
2020-09-01 | GSE103862 | GEO
Project description:Identifying immune correlates of protection and mechanisms of immunity accelerates and streamlines the development of vaccines. RTS,S/AS01E, the most advanced malaria vaccine, has moderate efficacy in African children. In contrast, immunization with sporozoites under antimalarial chemoprophylaxis (CPS immunization) can provide 100% sterile protection in naïve adults. We used systems biology approaches to identify correlates of vaccine-induced immunity based on transcriptomes of peripheral blood mononuclear cells from subjects immunized with RTS,S/AS01E or chemo-attenuated sporozoites stimulated with parasite antigens in vitro. Specifically, we used samples of subjects from two age cohorts and 3 African countries participating in an RTS,S/AS01E pediatric phase 3 trial and malaria-naïve subjects participating in a CPS trial. We identified both pre-immunization and post-immunization transcriptomic signatures correlating with protection. Signatures were validated in independent children and infants from the RTS,S/AS01E phase 3 trial and subjects from an independent CPS trial with high accuracies (>70%). Transcription modules revealed interferon, NF-B, TLR, and monocyte-related signatures associated with protection. Pre-immunization signatures suggest the potential for strategies to prime the immune system before vaccination towards improving vaccine immunogenicity and efficacy. Finally, signatures of protection could be useful to determine efficacy in clinical trials, accelerating vaccine candidate testing. Nevertheless, signatures should be tested more extensively across multiple cohorts and trials to demonstrate their universal predictive capacity.
2020-05-13 | GSE144826 | GEO
Project description:This clinical trial (NCT02252640) assesses the safety and immune responses to vaccination with experimental malaria vaccine candidates RTS,S/AS01, ChAd63 ME-TRAP and MVA ME-TRAP in different combinations. All healthy volunteers were recruited in England and administered the experimental malaria vaccines. Furthermore, volunteers were infected with malaria by mosquito bites, 12 weeks after the first vaccination to assess vaccine efficacy.
2020-09-01 | GSE103874 | GEO
Project description:RTS,S is the sole candidate vaccine shown to provide protection against infection to malaria-naive adults challenged with mosquito-borne homologous falciparum malaria and protection against infection and clinical and severe disease to volunteers in malaria-endemic Africa who were exposed to diverse Plasmodium falciparum strains. In this experiment we profiled gene expression in PBMCs after vaccination with the RTS,S candidate malaria vaccine in a controlled human malaria infection study. Subjects were vaccinated with three doses of the RTS,S candidate malaria vaccine. Blood samples for PBMC isolation and subsequent gene expression analysis were taken on day 0 (0m), day of the third vaccination (8w), 1 day post third vaccination (8w1d), 3 days post third vaccination (8w3d), the day of the infection (10w), 1 day post infection (10w1d), and 5 days post infection (10w5d). After infection the subjects were closely monitored for parasitemia. The response to the controlled infection was recorded as follows: no parasitemia (P, protected), parasitemia in the same time frame as the control group (NP, not protected), parasitemia later than the control group (DL, delayed). In addition to the experimental factors, a confounding factor was identified in the data analysis related to the use of a specific kit batch (Kit A or B).
2017-04-27 | E-MTAB-4629 | biostudies-arrayexpress
Project description:Total RNA sequencing of peripheral blood mononuclear cells (PBMC) from Tanzanian children from the Phase 3 trial of the RTS,S (Mosquirix) vaccine (ClinicalTrials.gov NCT00866619). At baseline (B0) children were between 5-17 months of age at baseline (B0), and were 32 months older at B32.
2020-02-05 | GSE134985 | GEO
Project description:Protein interaction analysis of Plasmodium falciparum circumsporozoite protein variants with human immunoproteins explains RTS,S vaccine efficacy in Ghana
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Project description:Comaprision of P.falciparum clinical isolates showing Uncomplicated disease with that shwoing complicated disease(Cerebral malaria) The experiment was designed to try and identify differences if any, at the genome level between P.falciparum isolates from patients with uncomplicated malaria vs. patients with complicated malaria (Cerebral malaria). The emphasis was to highlight possible amplifications/deletions in different regions of the parasite genome.
2017-01-06 | GSE77165 | GEO
Project description:Genome wide transcriptome analyses could reveal whether parasites causing severe malarial disease express different genes to those causing uncomplicated malaria. This knowledge could inform therapy and vaccine design targeting severe disease. Venous samples were collected from patients with severe (n=23) and uncomplicated (n=21) malaria attending a healthcare facility in Timika, Papua Province, Indonesia. This area has unstable malaria transmission with estimated annual parasite incidence of 450 per 1000 population and symptomatic illness in all ages. Severe malaria was defined as peripheral parasitaemia with at least one modified World Health Organization (WHO) criterion of severity. Erythrocytes were immediately isolated from whole blood, solubilised in RNA preservative and frozen. Libraries were 100 bp paired end sequenced on a 2500-HT Hiseq (Illumina) using RapidRun chemistry (Illumina).
2018-02-08 | E-MTAB-5860 | biostudies-arrayexpress
Project description:Optimize SNP genotyping probes and demonstrate a new P. falciparum microarray platform that includes CGH and resequencing probes on the same chip
2011-04-01 | GSE28287 | GEO