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3. Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis

Author

Pearson, Mark S, Tedla, Bemnet A, Becker, Luke, Nakajima, Rie, Jasinskas, Al, Mduluza, Takafira, Mutapi, Francisca, Oeuvray, Claude, Greco, Beatrice, Sotillo, Javier, Felgner, Philip L, and Loukas, Alex

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Vaccine Related, Digestive Diseases, Orphan Drug, Infectious Diseases, Biotechnology, Prevention, Immunization, Vector-Borne Diseases, Rare Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Good Health and Well Being, Animals, Antibodies, Helminth, Antigens, Helminth, Computational Biology, Disease Models, Animal, Epitope Mapping, Helminth Proteins, Host-Pathogen Interactions, Humans, Immunoglobulin G, Mice, Parasite Load, Praziquantel, Proteomics, Protozoan Vaccines, Schistosoma haematobium, Schistosomiasis haematobia, Vaccination, cystatin, praziquantel, proteome microarray, urogenital schistosomiasis, vaccine, immunomics, Immunology, Biochemistry and cell biology, Genetics
Abstract

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

Published
2021

6. Randomized, Placebo Controlled Trial of Experimental Hookworm Infection for Improving Gluten Tolerance in Celiac Disease

Author

Croese, John, Miller, Gregory C., Marquart, Louise, Llewellyn, Stacey, Gupta, Rohit, Becker, Luke, Clouston, Andrew D., Welch, Christine, Sidorenko, Julia, Wallace, Leanne, Visscher, Peter M., Remedios, Matthew L., McCarthy, James S., OʼRourke, Peter, Radford-Smith, Graham, Loukas, Alex, Norrie, Mark, Masson, John W., Gearry, Richard B., Rahman, Tony, and Giacomin, Paul R.

Published
2020
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7. Additional file 1 of The production of Necator americanus larvae for use in experimental human infection

Author

Chapman, Paul R., Llewellyn, Stacey, Jennings, Helen, Becker, Luke, Giacomin, Paul, McDougall, Rodney, Robson, Jennifer, Loukas, Alex, and McCarthy, James

Subjects
fluids and secretions, integumentary system, education, digestive, oral, and skin physiology, parasitic diseases
Abstract

Additional file 1: Stool DNA extraction and qPCR. Figure S1. A. Faecal hookworm PCR Cq values correlated to larval yield and over 16 months. B. Faecal hookworm PCR Cq values over time.

Published
2022
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8. Characterisation of tetraspanins from Schistosoma haematobium and evaluation of their potential as novel diagnostic markers

Author

Mekonnen, Gebeyaw G., primary, Tedla, Bemnet A., additional, Pearson, Mark S., additional, Becker, Luke, additional, Field, Matt, additional, Amoah, Abena S., additional, van Dam, Govert, additional, Corstjens, Paul L. A. M., additional, Mduluza, Takafira, additional, Mutapi, Francisca, additional, Loukas, Alex, additional, and Sotillo, Javier, additional

Published
2022
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9. Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study

Author

Pearson, Mark S, primary, Tedla, Bemnet A, additional, Mekonnen, Gebeyaw G, additional, Proietti, Carla, additional, Becker, Luke, additional, Nakajima, Rie, additional, Jasinskas, Al, additional, Doolan, Denise L, additional, Amoah, Abena S, additional, Knopp, Stefanie, additional, Rollinson, David, additional, Ali, Said M, additional, Kabole, Fatma, additional, Hokke, Cornelis H, additional, Adegnika, Akim A, additional, Field, Matt A, additional, van Dam, Govert, additional, Corstjens, Paul L A M, additional, Mduluza, Takafira, additional, Mutapi, Francisca, additional, Oeuvray, Claude, additional, Greco, Beatrice, additional, Chaiyadet, Sujittra, additional, Laha, Thewarach, additional, Cai, Pengfei, additional, McManus, Donald P, additional, Bottazzi, Maria Elena, additional, Felgner, Philip L, additional, Sotillo, Javier, additional, and Loukas, Alex, additional

Published
2021
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11. Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis

Author

Pearson, Mark S., primary, Tedla, Bemnet A., additional, Becker, Luke, additional, Nakajima, Rie, additional, Jasinskas, Al, additional, Mduluza, Takafira, additional, Mutapi, Francisca, additional, Oeuvray, Claude, additional, Greco, Beatrice, additional, Sotillo, Javier, additional, Felgner, Philip L., additional, and Loukas, Alex, additional

Published
2021
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15. Hookworms Evade Host Immunity by Secreting a Deoxyribonuclease to Degrade Neutrophil Extracellular Traps

Author

Bouchery, Tiffany, primary, Moyat, Mati, additional, Sotillo, Javier, additional, Silverstein, Solomon, additional, Volpe, Beatrice, additional, Coakley, Gillian, additional, Tsourouktsoglou, Theodora-Dorita, additional, Becker, Luke, additional, Shah, Kathleen, additional, Kulagin, Manuel, additional, Guiet, Romain, additional, Camberis, Mali, additional, Schmidt, Alfonso, additional, Seitz, Arne, additional, Giacomin, Paul, additional, Le Gros, Graham, additional, Papayannopoulos, Venizelos, additional, Loukas, Alex, additional, and Harris, Nicola L., additional

Published
2020
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17. In-depth proteomic characterization of Schistosoma haematobium: Towards the development of new tools for elimination

Author

Sotillo, Javier, primary, Pearson, Mark S., additional, Becker, Luke, additional, Mekonnen, Gebeyaw G., additional, Amoah, Abena S., additional, van Dam, Govert, additional, Corstjens, Paul L. A. M., additional, Murray, Janice, additional, Mduluza, Takafira, additional, Mutapi, Francisca, additional, and Loukas, Alex, additional

Published
2019
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18. Hookworm-Derived Metabolites Suppress Pathology in a Mouse Model of Colitis and Inhibit Secretion of Key Inflammatory Cytokines in Primary Human Leukocytes

Author

Wangchuk, Phurpa, primary, Shepherd, Catherine, additional, Constantinoiu, Constantin, additional, Ryan, Rachael Y. M., additional, Kouremenos, Konstantinos A., additional, Becker, Luke, additional, Jones, Linda, additional, Buitrago, Geraldine, additional, Giacomin, Paul, additional, Wilson, David, additional, Daly, Norelle, additional, McConville, Malcolm J., additional, Miles, John J., additional, and Loukas, Alex, additional

Published
2019
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19. Polypyridylruthenium(II) complexes exert anti-schistosome activity and inhibit parasite acetylcholinesterases

Author

Sundaraneedi, Madhu K., primary, Tedla, Bemnet A., additional, Eichenberger, Ramon M., additional, Becker, Luke, additional, Pickering, Darren, additional, Smout, Michael J., additional, Rajan, Siji, additional, Wangchuk, Phurpa, additional, Keene, F. Richard, additional, Loukas, Alex, additional, Collins, J. Grant, additional, and Pearson, Mark S., additional

Published
2017
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21. Of Monkeys and Men: Immunomic Profiling of Sera from Humans and Non-Human Primates Resistant to Schistosomiasis Reveals Novel Potential Vaccine Candidates

Author

Pearson, Mark S., primary, Becker, Luke, additional, Driguez, Patrick, additional, Young, Neil D., additional, Gaze, Soraya, additional, Mendes, Tiago, additional, Li, Xiao-Hong, additional, Doolan, Denise L., additional, Midzi, Nicholas, additional, Mduluza, Takafira, additional, McManus, Donald P., additional, Wilson, R. Alan, additional, Bethony, Jeffrey M., additional, Nausch, Norman, additional, Mutapi, Francisca, additional, Felgner, Philip L., additional, and Loukas, Alex, additional

Published
2015
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