Dataset Information

Antigen discovery in circulating extracellular vesicles from Plasmodium vivax patients

ABSTRACT: Plasmodium vivax is the most widely distributed human malaria parasite with 7 million annual clinical cases and 2.5 billion people living under risk of infection. Presently, there is an urgent need to discover new antigens for vaccination as only two vaccine candidates, both based on the Duffy Binding protein, are currently in clinical trials. Extracellular vesicles (EVs) are small membrane-bound vesicles involved in intercellular communication and initially described in reticulocytes, the host cell of P. vivax, as a selective disposal mechanism of the transferrin receptor (CD71) in the maturation of reticulocytes to erythrocytes. We have recently reported the proteomics identification of P. vivax proteins associated to circulating EVs in P. vivax patients using size exclusion chromatography followed by mass spectrometry. Parasite proteins, however, were detected in two out of ten patients and only three of them with more than one unique peptide (UP). To increase the signal, we have implemented the Direct Immuno-affinity Capture (DIC) technique to enrich in EVs derived from CD71-expressing cells. Remarkably, we identified parasite proteins in all patients totaling 48 proteins (24 identified with ≥2 UP) and including several previously identified P. vivax vaccine candidate antigens (MSP1, MSP3, MSP7, MSP9, Serine-repeat antigen 1, and HSP70) as well as several membrane, cytosolic and exported proteins. Notably, a member of the Plasmodium helical interspersed sub-telomeric (PHIST-c) family, previously shown to be a main component of the caveola vesicle complexes, was robustly detected in five out six analyzed patients. Humoral immune response analysis by luminex confirmed its antigenicity. Collectively, we showed that enrichment of EVs by CD71-DIC from plasma, allows a robust identification of P. vivax proteins. This study represents a major advance in identifying new antigens for vaccination against this human malaria parasite.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Plasmodium Vivax

TISSUE(S): Blood Plasma, Extracellular Vesicle

DISEASE(S): Malaria

SUBMITTER: Eva Borràs

LAB HEAD: Eduard Sabido

PROVIDER: PXD029439 | Pride | 2022-02-22

REPOSITORIES: Pride

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Publications

Antigen Discovery in Circulating Extracellular Vesicles From Plasmodium vivax Patients.

Aparici-Herraiz Iris I Gualdrón-López Melisa M Castro-Cavadía Carlos J CJ Carmona-Fonseca Jaime J Yasnot María Fernanda MF Fernandez-Becerra Carmen C Del Portillo Hernando A HA

Frontiers in cellular and infection microbiology 20220124

Plasmodium vivax is the most widely distributed human malaria parasite with 7 million annual clinical cases and 2.5 billion people living under risk of infection. There is an urgent need to discover new antigens for vaccination as only two vaccine candidates are currently in clinical trials. Extracellular vesicles (EVs) are small membrane-bound vesicles involved in intercellular communication and initially described in reticulocytes, the host cell of P. vivax, as a selective dispos ...[more]

PMID: 35141172

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Project description:Plasmodium vivax is the most geographically widespread human malaria parasite causing approximately 130-435 million infections annually. It is an economic burden in many parts of the world and poses a public health challenge along with the other Plasmodium sp. The biology of this parasite is very little understood. Emerging evidences of severe complications due to infections by this parasite provides an impetus to focus research on the same. Investigating this parasite directly from the infected patients is the most feasible way to study its biology and any pathogenic mechanisms which may exist. Gene expression studies of this parasite directly obtained from the patients has provided evidence of gene regulation resulting in varying amount of transcript levels in the different blood stages. However, the mechanisms regulating gene expression in malaria parasites are not well understood. Discovery of natural antisense transcripts (NATs) in P. falciparum has suggested that these might play an important role in regulating gene expression. We report here the genome-wide occurrence of NATs in P. vivax parasites from patients with differing clinical symptoms. A total of 1348 NATs against annotated gene loci have been detected using a custom designed strand specific microarray. Majority of NATs identified from this study shows positive correlation with the expression pattern of the sense transcript. Our data also shows condition specific expression patterns of varying S and AS transcript levels. Genes with AS transcripts enrich to various biological processes. This is the first report detailing the presence of NATs from clinical isolates of P. vivax. The data suggests differential regulation of gene expression in diverse clinical conditions and would lead to future detailed investigations of genome regulation. Plasmodium vivax isolates were collected from patients (n = 8) with differing clinical conditions.The patients exhibited symptoms categorized as un-complicated (n =1) or complicated malaria (n = 7). Criteria for determination of complicated disease were based on World Health Organization year 2010 guidelines. Microarray array based transcriptional profiling was carried out to detect prevalence of natural antisense transcripts.

Project description:Nilsson Bark SK, Ahmad R, Dantzler K, Lukens AK, De Niz M, Szucs MJ, Jin X, Cotton J, Hoffmann D, Bric-Furlong E, Oomen R, Parrington M, Milner D, Neafsey DE, Carr SA, Wirth DF, Marti M. Mol Cell Proteomics 2017. Despite recent efforts towards control and elimination, malaria remains a major public health problem worldwide. Plasmodium falciparum resistance against artemisinin, used in front line combination drugs, is on the rise, and the only approved vaccine shows limited efficacy. Combinations of novel and tailored drug and vaccine interventions are required to maintain the momentum of the current malaria elimination program. Current evidence suggests that strain-transcendent protection against malaria infection can be achieved using whole organism vaccination or with a polyvalent vaccine covering multiple antigens or epitopes. These approaches have been successfully applied to the human-infective sporozoite stage. Both systemic and tissue-specific pathology during infection with the human malaria parasite P. falciparum is caused by asexual blood stages. Tissue tropism and vascular sequestration are the result of specific binding interactions between antigens on the parasite-infected red blood cell (pRBC) surface and endothelial receptors. The major surface antigen and parasite ligand binding to endothelial receptors, PfEMP1 is encoded by about 60 variants per genome and shows high sequence diversity across strains. Apart from PfEMP1 and three additional variant surface antigen families RIFIN, STEVOR and SURFIN, systematic analysis of the infected red blood cell surface is lacking. Here we present the most comprehensive proteomic investigation of the parasitized red blood cell surface so far. Apart from the known variant surface antigens, we identified a set of putative single copy surface antigens with low sequence diversity, several of which are validated in a series of complementary experiments. Further functional and immunological investigation is underway to test these novel P. falciparum blood stage proteins as possible vaccine candidates.

Dataset Information

Antigen discovery in circulating extracellular vesicles from Plasmodium vivax patients

Publications

Antigen Discovery in Circulating Extracellular Vesicles From <i>Plasmodium vivax</i> Patients.

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