Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular Hallmarks of Naturally Acquired Immunity to Malaria

ABSTRACT: Immunity to malaria can be acquired through natural exposure to Plasmodium falciparum (Pf), but only after years of repeated infections. Typically, this immunity is acquired by adolescence and confers protection against disease, but not Pf infection per se. Efforts to understand the mechanisms of this immunity are integral to the development of a vaccine that would mimic the induction of adult immunity in children. The current study applies transcriptomic analyses to a cohort from the rural village of Kalifabougou, Mali, where Pf transmission is intense and seasonal. Signatures that correlate with protection from malaria may yield new hypotheses regarding the biological mechanisms through which malaria immunity is induced by natural Pf infection. The resulting datasets will be of considerable value in the urgent worldwide effort to develop a malaria vaccine that could prevent more than a million deaths annually.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52166 | GEO | 2013/11/08

SECONDARY ACCESSION(S): PRJNA227074

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Molecular Hallmarks of Naturally Acquired Immunity to Malaria

Project description:Immunity to malaria can be acquired through natural exposure to Plasmodium falciparum (Pf), but only after years of repeated infections. Typically, this immunity is acquired by adolescence and confers protection against disease, but not Pf infection per se. Efforts to understand the mechanisms of this immunity are integral to the development of a vaccine that would mimic the induction of adult immunity in children. The current study applies transcriptomic analyses to a cohort from the rural village of Kalifabougou, Mali, where Pf transmission is intense and seasonal. Signatures that correlate with protection from malaria may yield new hypotheses regarding the biological mechanisms through which malaria immunity is induced by natural Pf infection. The resulting datasets will be of considerable value in the urgent worldwide effort to develop a malaria vaccine that could prevent more than a million deaths annually. 108 samples; paired pre- and post-challenge for 54 individuals 198 samples; paired pre- and post-challenge for 99 individuals

2013-11-08 | E-GEOD-52166 | biostudies-arrayexpress

Transcription profiling of PfSPZ Malaria Vaccine trial subjects in a malaria endemic region

Project description:The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. The PfSPZ Vaccine trial in Mali was the first to evaluate the safety and efficacy of this vaccine in a malaria endemic region. Vaccinees received five doses of 2.7 X 105 irradiated sporozoites and the efficacy was measured against naturally occurring Pf Infections in Malian adults during the malaria transmission season.

2017-01-01 | GSE86308 | GEO

Plasmodium-specific atypical memory B cells upregulate markers of activation and co-stimulatory molecules indicative of cellular interaction with T cells in response to a febrile malaria infection in children and adults.

Project description:In naturally acquired immunity to malaria, antibodies that reliably protect are only acquired after years of repeated Plasmodium falciparum (Pf) infections. We have shown in Mali that this inefficiency in humoral immunity to malaria is associated with a large expansion of CD21loCD27- ‘atypical’ B cells (atBCs). The function of atBCs remains elusive, as they exhibit altered B cell receptor (BCR) signaling and when activated fail to secrete cytokines and antibodies. We set out to study the participation and function of malaria-specific atBCs during the immune response to a febrile malaria infection. Here, we show in a Mali cohort spanning infants to adults, that atBCs frequencies within the malaria and influenza-specific MBC compartment are comparable to the overall atBC frequency, showing that atBCs are not predominantly expanded within Pf-specific B cells. We performed a transcriptional analysis of Pf- and influenza-specific atBCs, actBC and MBCs and show that CXCL16, IL-6, IL-10, TNFα, IL12R and IL12R are uniquely upregulated in Pf-specific atBCs. Comparative transcriptomic and flow cytometric analysis before and after an acute malaria infection showed that after malaria, Pf-specific atBCs are transcriptionally most like the actBC subset, sharing many common features, such as activation of intracellular signaling pathways and expression of high levels of T-bet, FcRL5, Ki67 and CD86. Unique to Pf-specific atBCs was an upregulation of IL-5RA, CD38, CXCR3, TLR7, 9 and 10 after a febrile malaria episode. Our data shows that atBCs exhibit a surface marker profile that could facilitate cellular interaction with T cells in secondary lymphoid tissues.

2022-06-01 | GSE183744 | GEO

Transcription profiling of PfSPZ Malaria Vaccine trial subjects receiving a 3-dose regimen in a malaria endemic region

Project description:The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. Vaccinees received 3 doses of 1.8 X 106 irradiated sporozoites. Efficacy was measured by challenged by controlled human malaria infections (CHMI), and against naturally occurring Pf Infections in Malian adults during the malaria transmission season

2022-08-20 | GSE211599 | GEO

Transcription profiling of PfSPZ Vaccine trial subjects (US, malaria naïve) receiving a 3-dose or 5-dose regimen

Project description:The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. Vaccinees received either 3 doses of 1.8M irradiated sporozoites or 5 doses of 270K. Efficacy was measured by challenged by controlled human malaria infections (CHMI) at 3 weeks and 24 weeks after the last vaccine dose

2022-08-22 | GSE211626 | GEO

single-cell RNA-sequencing on human naïve and memory CD4+ T cells during Plasmodium falciparum infection

Project description:Plasmodium falciparum (Pf) malaria causes high rates of morbidity and mortality and lacks an effective vaccine. Clinical immunity develops in residents of malaria endemic regions which confers reduced clinical symptoms during infection and protects against severe disease. We hypothesized that understanding the immune mechanisms of clinical immunity could inform vaccine design to improve efficacy. We compared the peripheral blood cellular and humoral immune responses during Pf malaria infection between clinically susceptible and protected participants from a malaria endemic region in Malawi during a prospective 18-month longitudinal study. Participant classifications were defined by the number of recurrent clinical malaria episodes with susceptible participants having more than three while protected less than one episode during the study period. Protected participants exhibited higher immunoglobulin G (IgG) breadth and titers against Pf antigens, and greater antibody (Ab)-dependent Pf opsonization compared to susceptible participants, consistent with our classifications. Using high dimensional mass cytometry (CyTOF) and spectral flow cytometry, and single-cell transcriptomic analyses, we identified expanded memory CD4+ T cell clonotypes in the blood of protected participants undergoing malaria infection. These cells express a strong cytolytic T helper 1 effector program with transcripts encoding granzymes (A, B, H, M), granulysin, NKG7 and the ZEB2 master transcriptional regulator of terminally differentiated effector T cells. ZEB2+ memory CD4+ T cells were CD39hiTIGIThi and expressed multiple chemotactic and inhibitory receptors. Yet, their levels of several chemokine and checkpoint inhibitory receptors were reduced in protected compared to susceptible individuals. We propose that clonally expanded ZEB2+ cytolytic memory CD4+ Th1 cells could represent essential contributors to clinical immunity against Pf malaria infection.

2021-08-28 | GSE182536 | GEO

Immunogenomic profile at baseline predicts host susceptibility to clinical malaria

Project description:Host gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. To identify determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing, we analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with >2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint. We noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points. We also observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. This suggests that differences in apoptotic and inflammatory gene expression patterns can predict susceptibility to clinical malaria.

2023-06-29 | GSE234970 | GEO

Common asymptomatic and submicroscopic malaria infections in Western Thailand revealed in longitudinal molecular and serological studies: a challenge to malaria elimination.

Project description:Malaria is the most important vector-borne disease in Southeast Asia. In Thailand, malaria incidence has been in decline, with the annual parasite incidence dropping to 0.56 in 2007. The Myanmar-Thai border province of Tak is considered meso-endemic for malaria, and both Plasmodium vivax (Pv) and P. falciparum (Pf) are equally present. As part of the International Centers for Excellence in Malaria Research (ICEMR) - Southeast Asia project, malaria surveillance is conducted in Tak on both the healthy population and hospital patients, and parasite prevalence is reportedly <1%. However, little is known about the immuno-epidemiology associated with Pf and Pv infections in the region regarding the breadth and targets of the antibody response to the malaria parasites. Our hypothesis is that the serological profiles of the population will reflect the low parasite prevalence in Tak, showing little antibody reactivity to Pv and Pf. To examine this question, we developed a protein microarray displaying the top 500 most immunogenic antigens of these two Plasmodium species. We collected whole blood samples from healthy residents of Mae Salid Noi village during a Mass Blood Survey for malaria in the region. Whole blood was sent to UCI for qPCR and serology analysis. Blood plasma was probed on the protein microarray; genomic DNA was extracted from RBC pellets and screened by qPCR for infection confirmation and species identification. One-hundred percent (n=381) of serum samples were reactive to both Pv and Pf antigens, including all qPCR-negative samples.

2016-02-01 | GSE75593 | GEO

Antigen-stimulated PBMC transcriptional signatures of protection upon malaria sporozoite and RTS,S/AS01E immunizations

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

Molecular Hallmarks of Experimentally Acquired Immunity to Malaria [Pilot Study]

Project description:Sterile immunity to Plasmodium falciparum infection can be induced experimentally in humans after few exposures. An example is the induction of immunity using whole parasites by exposure of malaria-naive volunteers to infectious mosquito bites while using chloroquine prophylaxis (CPS immunization). Chloroquine kills blood-stage parasites but leaves liver-stage parasites unaffected, thereby exposing the liver-stage and early blood-stage antigens to the immune system. Upon subsequent challenge, volunteers are completely protected from infection, but protective efficacy decreases when fewer infectious mosquito bites are used for CPS immunization. Efforts to understand the mechanisms of this immunity, and how it differs from naturally-acquired immunity, may provide critical insights that could aid malaria vaccine development. In this pilot study, transcriptomic features are derived from blood samples collected before and after challenge with infectious mosquito bites. 12 samples; paired pre- and post-challenge for 5 individuals, plus two controls

2013-09-18 | E-GEOD-50957 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data