Proteomics

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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

Dataset's files

Source:
Action DRS
2020ME004_MEGU_001_01_20pto.pdResult Other
2020ME004_MEGU_001_01_20pto.raw Raw
2020ME004_MEGU_002_01_20pto.raw Raw
2020ME004_MEGU_003_01_20pto.raw Raw
2020ME004_MEGU_004_01_20pto.raw Raw
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Publications

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


<i>Plasmodium vivax</i> 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 <i>P. vivax</i>, as a selective dispos  ...[more]

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