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Monoclonal Antibodies Targeting an Opisthorchis viverrini Extracellular Vesicle Tetraspanin Protect Hamsters against Challenge Infection

Opisthorchis viverrini causes severe pathology in the bile ducts of infected human hosts, and chronic infection can culminate in bile duct cancer. The prevention of infection by vaccination would decrease opisthorchiasis-induced morbidity and mortality. The tetraspanin protein, Ov-TSP-2, is located...

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Autores principales: Phumrattanaprapin, Wuttipong, Pearson, Mark, Pickering, Darren, Tedla, Bemnet, Smout, Michael, Chaiyadet, Sujittra, Brindley, Paul J., Loukas, Alex, Laha, Thewarach
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310160/
https://www.ncbi.nlm.nih.gov/pubmed/34358156
http://dx.doi.org/10.3390/vaccines9070740
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author Phumrattanaprapin, Wuttipong
Pearson, Mark
Pickering, Darren
Tedla, Bemnet
Smout, Michael
Chaiyadet, Sujittra
Brindley, Paul J.
Loukas, Alex
Laha, Thewarach
author_facet Phumrattanaprapin, Wuttipong
Pearson, Mark
Pickering, Darren
Tedla, Bemnet
Smout, Michael
Chaiyadet, Sujittra
Brindley, Paul J.
Loukas, Alex
Laha, Thewarach
author_sort Phumrattanaprapin, Wuttipong
collection PubMed
description Opisthorchis viverrini causes severe pathology in the bile ducts of infected human hosts, and chronic infection can culminate in bile duct cancer. The prevention of infection by vaccination would decrease opisthorchiasis-induced morbidity and mortality. The tetraspanin protein, Ov-TSP-2, is located on the membrane of secreted extracellular vesicles (EVs), and is a candidate antigen for inclusion in a subunit vaccine. To address the role of anti-Ov-TSP-2 antibodies in protection, we assessed the protective capacity of anti-Ov-TSP-2 monoclonal antibodies (mAbs) against opisthorchiasis. Two anti-TSP-2 IgM mAbs, 1D6 and 3F5, and an isotype control were passively transferred to hamsters, followed by parasite challenge one day later. Hamsters that received 3F5 had 74.5% fewer adult flukes and 67.4% fewer eggs per gram of feces compared to hamsters that received the control IgM. Both 1D6 and 3F5 (but not the control IgM) blocked the uptake of fluke EVs by human bile duct epithelial cells in vitro. This is the first report of passive immunization against human liver fluke infection, and the findings portend the feasibility of antibody-directed therapies for liver fluke infection, bolstering the selection of TSPs as components of a subunit vaccine for opisthorchiasis and fluke infections generally.
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spelling pubmed-83101602021-07-25 Monoclonal Antibodies Targeting an Opisthorchis viverrini Extracellular Vesicle Tetraspanin Protect Hamsters against Challenge Infection Phumrattanaprapin, Wuttipong Pearson, Mark Pickering, Darren Tedla, Bemnet Smout, Michael Chaiyadet, Sujittra Brindley, Paul J. Loukas, Alex Laha, Thewarach Vaccines (Basel) Article Opisthorchis viverrini causes severe pathology in the bile ducts of infected human hosts, and chronic infection can culminate in bile duct cancer. The prevention of infection by vaccination would decrease opisthorchiasis-induced morbidity and mortality. The tetraspanin protein, Ov-TSP-2, is located on the membrane of secreted extracellular vesicles (EVs), and is a candidate antigen for inclusion in a subunit vaccine. To address the role of anti-Ov-TSP-2 antibodies in protection, we assessed the protective capacity of anti-Ov-TSP-2 monoclonal antibodies (mAbs) against opisthorchiasis. Two anti-TSP-2 IgM mAbs, 1D6 and 3F5, and an isotype control were passively transferred to hamsters, followed by parasite challenge one day later. Hamsters that received 3F5 had 74.5% fewer adult flukes and 67.4% fewer eggs per gram of feces compared to hamsters that received the control IgM. Both 1D6 and 3F5 (but not the control IgM) blocked the uptake of fluke EVs by human bile duct epithelial cells in vitro. This is the first report of passive immunization against human liver fluke infection, and the findings portend the feasibility of antibody-directed therapies for liver fluke infection, bolstering the selection of TSPs as components of a subunit vaccine for opisthorchiasis and fluke infections generally. MDPI 2021-07-05 /pmc/articles/PMC8310160/ /pubmed/34358156 http://dx.doi.org/10.3390/vaccines9070740 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Phumrattanaprapin, Wuttipong
Pearson, Mark
Pickering, Darren
Tedla, Bemnet
Smout, Michael
Chaiyadet, Sujittra
Brindley, Paul J.
Loukas, Alex
Laha, Thewarach
Monoclonal Antibodies Targeting an Opisthorchis viverrini Extracellular Vesicle Tetraspanin Protect Hamsters against Challenge Infection
title Monoclonal Antibodies Targeting an Opisthorchis viverrini Extracellular Vesicle Tetraspanin Protect Hamsters against Challenge Infection
title_full Monoclonal Antibodies Targeting an Opisthorchis viverrini Extracellular Vesicle Tetraspanin Protect Hamsters against Challenge Infection
title_fullStr Monoclonal Antibodies Targeting an Opisthorchis viverrini Extracellular Vesicle Tetraspanin Protect Hamsters against Challenge Infection
title_full_unstemmed Monoclonal Antibodies Targeting an Opisthorchis viverrini Extracellular Vesicle Tetraspanin Protect Hamsters against Challenge Infection
title_short Monoclonal Antibodies Targeting an Opisthorchis viverrini Extracellular Vesicle Tetraspanin Protect Hamsters against Challenge Infection
title_sort monoclonal antibodies targeting an opisthorchis viverrini extracellular vesicle tetraspanin protect hamsters against challenge infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310160/
https://www.ncbi.nlm.nih.gov/pubmed/34358156
http://dx.doi.org/10.3390/vaccines9070740
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