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Phase 1 Trial With Challenge to Assess the Safety and Biomarkers of Protection in Malaria-naive Adults of Immunization Via Mosquito Bite With Radiation-Attenuated Plasmodium Falciparum Sporozoites (IMRAS) - Day 140-147

ABSTRACT: Phase 1 Trial With Challenge to Assess the Safety and Biomarkers of Protection in Malaria-naive Adults of Immunization Via Mosquito Bite With Radiation-Attenuated Plasmodium Falciparum Sporozoites (IMRAS) - Day 140-147

PROVIDER: PRJNA793032 | ENA |

REPOSITORIES: ENA

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Phase 1 Trial With Challenge to Assess the Safety and Biomarkers of Protection in Malaria-naive Adults of Immunization Via Mosquito Bite With Radiation-Attenuated Plasmodium Falciparum Sporozoites (IMRAS) - Day 140-147

Project description:This study is to assess the safety, tolerability, and biomarkers of protection in healthy malaria-naive adults, who will receive bites from Anopheles stephensi mosquitoes either infected with Plasmodium falciparum Sporozoites (PfRAS) (true-immunization) or noninfected (mock-immunization).

2022-12-31 | GSE192757 | GEO

2022-12-31 | GSE192756 | GEO

2022-01-27 | GSE116619 | GEO

Plasmodium berghei PbeIK2KO sporozoites

Project description:Malaria sporozoites, the form transmitted by mosquitoes, are quiescent while in the insect salivary glands. It is only after the sporozoites are deposited in the hostâs skin, migrate to the liver and infect hepatocytes that the parasites continue the life cycle. We show that the sporozoite latency is an active process that requires phosphorylation of the eukaryotic initiation factor-2Î± (eIF2Î±) by a sporozoite-specific kinase. Inactivation of the kinase gene leads to an overall enhancement of protein synthesis including of silenced liver stage proteins, and inhibits transmission of malaria. Specific inhibition of the eIF2Î± phosphatase by salubrinal has the opposite effect. Thus, to prevent premature transformation into liver stages, Plasmodium sporozoites exploit the same mechanism that regulates stress responses in mammalian cells. 4 samples overall, 2 wt and 2 KO (PbeIK2 knockout) samples

2010-05-16 | E-GEOD-16259 | biostudies-arrayexpress

Plasmodium berghei PbeIK2KO sporozoites

Project description:Malaria sporozoites, the form transmitted by mosquitoes, are quiescent while in the insect salivary glands. It is only after the sporozoites are deposited in the host’s skin, migrate to the liver and infect hepatocytes that the parasites continue the life cycle. We show that the sporozoite latency is an active process that requires phosphorylation of the eukaryotic initiation factor-2α (eIF2α) by a sporozoite-specific kinase. Inactivation of the kinase gene leads to an overall enhancement of protein synthesis including of silenced liver stage proteins, and inhibits transmission of malaria. Specific inhibition of the eIF2α phosphatase by salubrinal has the opposite effect. Thus, to prevent premature transformation into liver stages, Plasmodium sporozoites exploit the same mechanism that regulates stress responses in mammalian cells.

2009-07-01 | GSE16259 | GEO

IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS.

Project description:BackgroundImmunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides >90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.MethodsThe ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.ResultsThere was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.ConclusionsThese studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.Trial registrationClinicalTrials.gov NCT01994525.

| S-EPMC8378721 | biostudies-literature

Gene expression affected by miR-147

Project description:The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer progression and may promote resistance to therapy. An analysis of patients (n = 71) profiled with both gene expression and a global microRNA assessment (~ 415 miRs) identified miR-147 as highly anti-correlated with an EMT gene expression signature score and postulated to reverse EMT (MET).We have found that miR-147 induced cancer cells to undergo MET phenotypically. It's necessary to investigate the genes affected by miR-147 to understand the mechanism. RNA extracted from miR-147 and non-coding miR transiently transfected HCT116 cells; gene expression then assayed using the Affymetrix GeneChip U133 Plus2.0 platform.

2014-11-01 | E-GEOD-51875 | biostudies-arrayexpress

Bacillus thuringiensis strain:147 | isolate:147

Project description:Bacillus thuringiensis strain:147 | isolate:147 Genome sequencing and assembly

| PRJNA288912 | ENA

Gene expression affected by miR-147

2014-11-01 | GSE51875 | GEO

Project description:Phase 1 Trial With Challenge to Assess the Safety and Biomarkers of Protection in Malaria-naive Adults of Immunization Via Mosquito Bite With Radiation-Attenuated Plasmodium Falciparum Sporozoites (IMRAS) - Day 31-126

| PRJNA793034 | ENA

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