Biology subjects

Tedla, B. A.

Publications and source records attributed to Tedla, B. A..

2 recordsLinked to original sources

bioRxiv2020

Schistosoma haematobium 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 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-tranferase, saposins 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.

microbiology↗

bioRxiv2020

Vaccination with Schistosoma mansoni cholinesterases reduces parasite burden and egg viability in a mouse model of schistosomiasis

Schistosomiasis is a neglected tropical disease which kills 300,000 people every year in developing countries and there is no vaccine. Recently, we have shown that cholinesterases (ChEs) - enzymes that regulate neurotransmission - from Schistosoma mansoni are expressed on the tegument and present in the excretory/secretory products of schistosomula and adult worms, and are essential for parasite survival in the definitive host, highlighting their utility as potential schistosomiasis vaccine targets. When treated in vitro with anti-SmChE IgG, both schistosomula and adult worms displayed significantly decreased ChE activity, which eventually resulted in parasite death. Vaccination with individual SmChEs, or a combination of all three SmChEs, significantly reduced worm burdens in two independent trials compared to controls. Liver egg burdens were significantly decreased for all vaccinated mice across both trials (13% - 46%) except for those vaccinated with SmAChE1 in trial 1. Egg viability, as determined by egg hatching from liver homogenates, was significantly reduced in the groups vaccinated with the SmChE cocktail (40%) and SmAChE2 (46%). Further, surviving worms from each vaccinated group were significantly stunted and depleted of glycogen stores, compared to controls. These results suggest that SmChEs could be incorporated into a vaccine against schistosomiasis to reduce the pathology and transmission of this debilitating disease.

microbiology↗