Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis
Despite the enormous morbidity attributed to schistosomiasis, there is still no vaccine to combat the disease for the hundreds of millions of infected people. The anthelmintic drug, praziquantel, is the mainstay treatment option, although its molecular mechanism of action remains poorly defined. Pra...
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Frontiers Media S.A.
2021-05-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.663041/full |
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doaj-58e793b9da6441c9a8a7d8fd0a89b538 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mark S. Pearson Bemnet A. Tedla Luke Becker Rie Nakajima Al Jasinskas Takafira Mduluza Takafira Mduluza Francisca Mutapi Francisca Mutapi Claude Oeuvray Beatrice Greco Javier Sotillo Javier Sotillo Philip L. Felgner Alex Loukas |
spellingShingle |
Mark S. Pearson Bemnet A. Tedla Luke Becker Rie Nakajima Al Jasinskas Takafira Mduluza Takafira Mduluza Francisca Mutapi Francisca Mutapi Claude Oeuvray Beatrice Greco Javier Sotillo Javier Sotillo Philip L. Felgner Alex Loukas Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis Frontiers in Immunology cystatin praziquantel proteome microarray urogenital schistosomiasis vaccine immunomics |
author_facet |
Mark S. Pearson Bemnet A. Tedla Luke Becker Rie Nakajima Al Jasinskas Takafira Mduluza Takafira Mduluza Francisca Mutapi Francisca Mutapi Claude Oeuvray Beatrice Greco Javier Sotillo Javier Sotillo Philip L. Felgner Alex Loukas |
author_sort |
Mark S. Pearson |
title |
Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis |
title_short |
Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis |
title_full |
Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis |
title_fullStr |
Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis |
title_full_unstemmed |
Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis |
title_sort |
immunomics-guided antigen discovery for praziquantel-induced vaccination in urogenital human schistosomiasis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-05-01 |
description |
Despite the enormous morbidity attributed to schistosomiasis, there is still no vaccine to combat the disease for the hundreds of millions of infected people. The anthelmintic drug, praziquantel, is the mainstay treatment option, although its molecular mechanism of action remains poorly defined. Praziquantel treatment damages the outermost surface of the parasite, the tegument, liberating surface antigens from dying worms that invoke a robust immune response which in some subjects results in immunologic resistance to reinfection. Herein we term this phenomenon Drug-Induced Vaccination (DIV). To identify the antigenic targets of DIV antibodies in urogenital schistosomiasis, we constructed a recombinant proteome array consisting of approximately 1,000 proteins informed by various secretome datasets including validated proteomes and bioinformatic predictions. Arrays were screened with sera from human subjects treated with praziquantel and shown 18 months later to be either reinfected (chronically infected subjects, CI) or resistant to reinfection (DIV). IgG responses to numerous antigens were significantly elevated in DIV compared to CI subjects, and indeed IgG responses to some antigens were completely undetectable in CI subjects but robustly recognized by DIV subjects. One antigen in particular, a cystatin cysteine protease inhibitor stood out as a unique target of DIV IgG, so recombinant cystatin was produced, and its vaccine efficacy assessed in a heterologous Schistosoma mansoni mouse challenge model. While there was no significant impact of vaccination with adjuvanted cystatin on adult worm numbers, highly significant reductions in liver egg burdens (45-55%, P<0.0001) and intestinal egg burdens (50-54%, P<0.0003) were achieved in mice vaccinated with cystatin in two independent trials. This study has revealed numerous antigens that are targets of DIV antibodies in urogenital schistosomiasis and offer promise as subunit vaccine targets for a drug-linked vaccination approach to controlling schistosomiasis. |
topic |
cystatin praziquantel proteome microarray urogenital schistosomiasis vaccine immunomics |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.663041/full |
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doaj-58e793b9da6441c9a8a7d8fd0a89b5382021-05-25T13:44:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-05-011210.3389/fimmu.2021.663041663041Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human SchistosomiasisMark S. Pearson0Bemnet A. Tedla1Luke Becker2Rie Nakajima3Al Jasinskas4Takafira Mduluza5Takafira Mduluza6Francisca Mutapi7Francisca Mutapi8Claude Oeuvray9Beatrice Greco10Javier Sotillo11Javier Sotillo12Philip L. Felgner13Alex Loukas14Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, AustraliaCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, AustraliaVaccine Research and Development Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, United StatesVaccine Research and Development Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, United StatesDepartment of Biotechnology and Biochemistry, University of Zimbabwe, Harare, ZimbabweTIBA Partnership, NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA) at the University of Edinburgh based in Harare (TIBA Zimbabwe), Harare, ZimbabweInstitute of Immunology and infection Research, Ashworth Laboratories, Edinburgh, United KingdomTIBA Partnership, NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA) at the University of Edinburgh, Edinburgh, United KingdomTIBA Partnership, NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA) at the University of Edinburgh, Edinburgh, United KingdomGlobal Health Institute of Merck, Ares Trading S.A., a subsidiary of Merck KGaA (Darmstadt, Germany), Eysins, SwitzerlandCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, AustraliaParasitology Reference and Research Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, SpainVaccine Research and Development Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, United StatesCentre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, AustraliaDespite the enormous morbidity attributed to schistosomiasis, there is still no vaccine to combat the disease for the hundreds of millions of infected people. The anthelmintic drug, praziquantel, is the mainstay treatment option, although its molecular mechanism of action remains poorly defined. Praziquantel treatment damages the outermost surface of the parasite, the tegument, liberating surface antigens from dying worms that invoke a robust immune response which in some subjects results in immunologic resistance to reinfection. Herein we term this phenomenon Drug-Induced Vaccination (DIV). To identify the antigenic targets of DIV antibodies in urogenital schistosomiasis, we constructed a recombinant proteome array consisting of approximately 1,000 proteins informed by various secretome datasets including validated proteomes and bioinformatic predictions. Arrays were screened with sera from human subjects treated with praziquantel and shown 18 months later to be either reinfected (chronically infected subjects, CI) or resistant to reinfection (DIV). IgG responses to numerous antigens were significantly elevated in DIV compared to CI subjects, and indeed IgG responses to some antigens were completely undetectable in CI subjects but robustly recognized by DIV subjects. One antigen in particular, a cystatin cysteine protease inhibitor stood out as a unique target of DIV IgG, so recombinant cystatin was produced, and its vaccine efficacy assessed in a heterologous Schistosoma mansoni mouse challenge model. While there was no significant impact of vaccination with adjuvanted cystatin on adult worm numbers, highly significant reductions in liver egg burdens (45-55%, P<0.0001) and intestinal egg burdens (50-54%, P<0.0003) were achieved in mice vaccinated with cystatin in two independent trials. This study has revealed numerous antigens that are targets of DIV antibodies in urogenital schistosomiasis and offer promise as subunit vaccine targets for a drug-linked vaccination approach to controlling schistosomiasis.https://www.frontiersin.org/articles/10.3389/fimmu.2021.663041/fullcystatinpraziquantelproteome microarrayurogenital schistosomiasisvaccineimmunomics |