Schistosoma haematobiumextracellular vesicle proteins confer protection in a heterologous model of schistosomiasis

Abstract

29Helminth parasites release extracellular vesicles which interact with the surrounding host 30 tissues, mediating host-parasite communication and other fundamental processes of 31 parasitism. As such, vesicle proteins present attractive targets for the development of 32 novel intervention strategies to control these parasites and the diseases they cause. Herein, 33 we describe the first proteomic analysis by LC-MS/MS of two types of extracellular 34 vesicles (exosome-like, 120k pellet vesicles and microvesicle-like, 15k pellet vesicles) 35 from adult Schistosoma haematobium worms. A total of 57 and 330 proteins were 36 identified in the 120k pellet vesicles and larger 15k pellet vesicles, respectively, and some 37 of the most abundant molecules included homologues of known helminth vaccine and 38 diagnostic candidates such as Sm-TSP2, Sm23, glutathione S-tranferase, saposins and 39 aminopeptidases. Tetraspanins were highly represented in the analysis and found in both 40 vesicle types. Vaccination of mice with recombinant versions of three of these 41 tetraspanins induced protection in a heterologous challenge (S. mansoni) model of 42 infection, resulting in significant reductions (averaged across two independent trials) in 43 liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These 44 findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer 45 protection and highlight the potential that extracellular vesicle surface proteins offer as 46 anti-helminth vaccines.47 48 Introduction 52Schistosomiasis is the second most important parasitic disease, only after malaria, 53 in terms of social, economic and public health impact [1]. Schistosoma haematobium, the 54 causative agent of urogenital schistosomiasis, is highly prevalent in 53 Middle East and 55 African countries [1] and it is also sporadically seen in India [2] and France [3]. Urogenital 56 schistosomiasis affects more than 90 million people, mostly in sub-Saharan Africa where 57 180 million inhabitants are at risk, and is responsible for 150,000 deaths per year [4]. 58Furthermore, the most common complications associated with this disease include 59 schistosomal haematuria, bladder wall pathology, hydronephrosis, and dysuria [4]. 60The current control programs against schistosomiasis are aimed at reducing the 61 morbidity caused by the parasite by regularly treating infected populations with 62 praziquantel [5]. Despite the efforts made to control this devastating disease, 63 schistosomiasis is still spreading to new geographical areas [3,6]. Furthermore, 64 praziquantel has shown reduced efficacy in field studies [7] and is not effective against 65 the immature stages of the parasite [8,9]. Hence, a vaccine that reduces disease severity 66 and/or reduces transmission is needed to control and eliminate schistosomiasis [10,11]. 67Despite efforts over decades, there is no licensed vaccine [1,12]. Even though various 68 vaccine candidates have advanced into clinical trials targeting Schistosoma mansoni, ...

Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines

“…The impact of the vaccine on infection with S. haematobium will also be assessed although this will be exploratory given that potential cross-protection against this species is not yet proven. There is, however, some cause for optimism as recombinant versions of three S. haematobium extracellular vesicles (EV)-derived tetraspanins (including the S. haematobium homologue of Sm-TSP-2) were recently shown to induce protection, albeit moderate, in terms of reduced liver and intestinal eggs in a heterologous vaccine/challenge ( S. mansoni ) model of infection [ 80 ].…”