Orally administered Bacillus spores expressing an extracellular vesicle-derived tetraspanin protect hamsters against challenge infection with carcinogenic human liver fluke

Phumrattanaprapin, Wuttipong, Chaiyadet, Sujittra, Brindley, Paul J., Pearson, Mark, Smout, Michael J., Loukas, Alex, and Laha, Thewarach (2021) Orally administered Bacillus spores expressing an extracellular vesicle-derived tetraspanin protect hamsters against challenge infection with carcinogenic human liver fluke. Journal of Infectious Diseases, 223 (8). pp. 1445-1455.

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View at Publisher Website: https://doi.org/10.1093/infdis/jiaa516
 
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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.

Item ID: 67552
Item Type: Article (Research - C1)
ISSN: 1537-6613
Keywords: oral vaccine, Bacillus subtilis, spore, Opisthorchis viverrini, tetraspanin, IgA
Copyright Information: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Funders: Thailand Research Fund (TRF), National Cancer Institute (NCI), National Institutes of Health (NIH), National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: TRF grant number PHD/0163/2561, NIH grant number 2R01CA164719-06A1, NHMRC grant number 1117504, NHMRC grant number 1132975
Date Deposited: 06 Jul 2021 04:51
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 100%
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