Schistosoma haematobium extracellular vesicle proteins confer protection in a heterologous model of schistosomiasis

Mekonnen, Gebeyaw G., Tedla, Bemnet A., Pickering, Darren, Becker, Luke, Wang, Lei, Zhan, Bin, Bottazzi, Maria Elena, Loukas, Alex, Sotillo, Javier, and Pearson, Mark S. (2020) Schistosoma haematobium extracellular vesicle proteins confer protection in a heterologous model of schistosomiasis. Vaccines, 8 (3). 416.

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Abstract

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, 120k pellet vesicles and microvesicle-like, 15k pellet vesicles) from adult Schistosoma haematobium worms. A total of 57 and 330 proteins were identified in the 120k pellet vesicles and larger 15k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such as Sm-TSP2, Sm23, 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 (S. mansoni) 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.

Item ID: 66733
Item Type: Article (Research - C1)
ISSN: 2076-393X
Keywords: Extracellular vesicles, Schistosomiasis, Tetraspanin, Vaccine
Copyright Information: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Funders: National Health and Medical Research Council Australia (NHMRC), James Cook University (JCU), Australian Institute of Tropical Health and Medicine (AITHM)
Projects and Grants: NHMRC program grant APP1037304, NHMRC Senior Principal Research Fellowship (APP1117504), JCU Postgraduate Scholarship, AITHM Postgraduate Scholarship
Date Deposited: 18 May 2021 04:08
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 100%
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