Orally Administered Bacillus Spores Expressing an Extracellular Vesicle-Derived Tetraspanin Protect Hamsters Against Challenge Infection With Carcinogenic Human Liver Fluke. (19th August 2020)

• Record Type: Journal Article
• Authors: Phumrattanaprapin, Wuttipong; Chaiyadet, Sujittra; Brindley, Paul J; Pearson, Mark; Smout, Michael J; Loukas, Alex; Laha, Thewarach
• Is Part Of: Journal of infectious diseases. Volume 223:Number 8(2021)
• Page Start: 1445
• Page End: 1455
• Publication Date: 2020-08-19
• Subjects: oral vaccine -- Bacillus subtilis -- spore -- Opisthorchis viverrini -- tetraspanin -- IgA; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa516
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: The human liver fluke Opisthorchis viverrini is a food-borne trematode that causes hepatobiliary disease in humans throughout Southeast Asia. People become infected by consuming raw or undercooked fish containing metacercariae. Development of a vaccine to prevent or minimize pathology would decrease the risk of severe morbidity, including the development of bile duct cancer. Methods: We produced an oral vaccine based on recombinant Bacillus subtilis spores expressing the large extracellular loop (LEL) of O. viverrini tetraspanin-2 ( Ov -TSP-2), a protein that is abundant on the surface of O. viverrini secreted extracellular vesicles (EVs). Recombinant spores expressing Ov -TSP-2-LEL were orally administered to hamsters prior to challenge infection with O. viverrini metacercariae. Results: Vaccinated hamsters generated serum IgG as well as bile IgG and IgA responses to Ov -TSP-2-LEL, and serum IgG from vaccinated hamsters blocked the uptake of fluke EVs by a human bile duct epithelial cell line. Vaccinated hamsters had 56% reductions in both adult flukes and fecal eggs compared to the control group. Conclusions: These findings indicate that oral vaccination of hamsters with recombinant B. subtilis spores expressing Ov -TSP-2-LEL is efficacious at reducing infection intensity and could form the basis of a vaccine for control of carcinogenic liver fluke infection in humans. Abstract : Infection with the liver fluke Opisthorchis viverrini is a risk factor for bile duct cancer in Southeast Asia. We describe an oral vaccine that interrupts host-parasite crosstalk via extracellular vesicles and induces partial protection in an animal model of opisthorchiasis.