<i>Schistosoma haematobium</i> Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis

Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host–parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to contro...

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Main Authors: Gebeyaw G. Mekonnen, Bemnet A. Tedla, Darren Pickering, Luke Becker, Lei Wang, Bin Zhan, Maria Elena Bottazzi, Alex Loukas, Javier Sotillo, Mark S. Pearson
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/8/3/416
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author Gebeyaw G. Mekonnen
Bemnet A. Tedla
Darren Pickering
Luke Becker
Lei Wang
Bin Zhan
Maria Elena Bottazzi
Alex Loukas
Javier Sotillo
Mark S. Pearson
author_facet Gebeyaw G. Mekonnen
Bemnet A. Tedla
Darren Pickering
Luke Becker
Lei Wang
Bin Zhan
Maria Elena Bottazzi
Alex Loukas
Javier Sotillo
Mark S. Pearson
author_sort Gebeyaw G. Mekonnen
collection DOAJ
description Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host–parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Herein, we describe the first proteomic analysis by LC-MS/MS of two types of extracellular vesicles (exosome-like, 120 k pellet vesicles and microvesicle-like, 15 k pellet vesicles) from adult <i>Schistosoma haematobium</i> worms. A total of 57 and 330 proteins were identified in the 120 k pellet vesicles and larger 15 k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such as <i>Sm</i>-TSP2, <i>Sm</i>23, glutathione S-transferase, saponins and aminopeptidases. Tetraspanins were highly represented in the analysis and found in both vesicle types. Vaccination of mice with recombinant versions of three of these tetraspanins induced protection in a heterologous challenge (<i>S. mansoni</i>) model of infection, resulting in significant reductions (averaged across two independent trials) in liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer protection and highlight the potential that extracellular vesicle surface proteins offer as anti-helminth vaccines.
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spelling doaj.art-baa5973d15bd49dda81d904b1b6ac26e2023-11-20T07:53:05ZengMDPI AGVaccines2076-393X2020-07-018341610.3390/vaccines8030416<i>Schistosoma haematobium</i> Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of SchistosomiasisGebeyaw G. Mekonnen0Bemnet A. Tedla1Darren Pickering2Luke Becker3Lei Wang4Bin Zhan5Maria Elena Bottazzi6Alex Loukas7Javier Sotillo8Mark S. Pearson9Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, AustraliaTexas Children’s Hospital Center for Vaccine Development, Department of Pediatrics and National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USATexas Children’s Hospital Center for Vaccine Development, Department of Pediatrics and National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USATexas Children’s Hospital Center for Vaccine Development, Department of Pediatrics and National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USACentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns 4878, Queensland, AustraliaHelminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host–parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Herein, we describe the first proteomic analysis by LC-MS/MS of two types of extracellular vesicles (exosome-like, 120 k pellet vesicles and microvesicle-like, 15 k pellet vesicles) from adult <i>Schistosoma haematobium</i> worms. A total of 57 and 330 proteins were identified in the 120 k pellet vesicles and larger 15 k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such as <i>Sm</i>-TSP2, <i>Sm</i>23, glutathione S-transferase, saponins and aminopeptidases. Tetraspanins were highly represented in the analysis and found in both vesicle types. Vaccination of mice with recombinant versions of three of these tetraspanins induced protection in a heterologous challenge (<i>S. mansoni</i>) model of infection, resulting in significant reductions (averaged across two independent trials) in liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer protection and highlight the potential that extracellular vesicle surface proteins offer as anti-helminth vaccines.https://www.mdpi.com/2076-393X/8/3/416schistosomiasisextracellular vesiclestetraspaninvaccine
spellingShingle Gebeyaw G. Mekonnen
Bemnet A. Tedla
Darren Pickering
Luke Becker
Lei Wang
Bin Zhan
Maria Elena Bottazzi
Alex Loukas
Javier Sotillo
Mark S. Pearson
<i>Schistosoma haematobium</i> Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis
Vaccines
schistosomiasis
extracellular vesicles
tetraspanin
vaccine
title <i>Schistosoma haematobium</i> Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis
title_full <i>Schistosoma haematobium</i> Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis
title_fullStr <i>Schistosoma haematobium</i> Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis
title_full_unstemmed <i>Schistosoma haematobium</i> Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis
title_short <i>Schistosoma haematobium</i> Extracellular Vesicle Proteins Confer Protection in a Heterologous Model of Schistosomiasis
title_sort i schistosoma haematobium i extracellular vesicle proteins confer protection in a heterologous model of schistosomiasis
topic schistosomiasis
extracellular vesicles
tetraspanin
vaccine
url https://www.mdpi.com/2076-393X/8/3/416
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