Antivenomic Assessment of the Immunological Reactivity of EchiTAb-Plus-ICP, an Antivenom for the Treatment of Snakebite Envenoming in Sub-Saharan Africa

Juan J. Calvete Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Pedro Cid Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Libia Sanz Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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álvaro Segura Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Mauren Villalta Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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María Herrera Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Guillermo León Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Robert Harrison Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Nandul Durfa Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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Abdusalami Nasidi Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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R. David G. Theakston Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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David A. Warrell Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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José María Gutiérrez Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica; Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Federal Ministry of Health, Abuja, Nigeria; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

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The immunoreactivity of EchiTAb-Plus-ICP, an antivenom developed for the treatment of snakebite envenoming in sub-Saharan Africa, to venoms of seven Echis and Bitis species, was assessed by “antivenomics.” This proteomic approach is based on the ability of an antivenom to immunodeplete homologous or heterologous venom proteins. Our results show an extensive cross-reactivity of this antivenom against all Echis and Bitis venoms studied, as revealed by the complete immunodepletion of the majority of venom components, including metalloproteinases, serine proteinases, C-type lectin-like proteins, some phospholipases A2 and L-amino acid oxidase. However, some phospholipases A2, disintegrins and proteinase inhibitors were immunodepleted to only a partial extent. These results support the hypothesis that immunizing horses with a mixture of the venoms of Echis ocellatus, Bitis arietans, and Naja nigricollis generates antibodies capable of recognizing the majority of components of medically-relevant homologous and heterologous viperid venoms of the genera Bitis and Echis from sub-Saharan Africa.

Author Notes

*Address correspondence to Juan J. Calvete, Instituto de Biomedicina de Valencia, C.S.I.C., Jaume Roig 11, 46010 Valencia, Spain. E-mail: jcalvete@ibv.csic.es

Financial support: This study was supported by Vicerrectoría de Investigación, Universidad de Costa Rica (project 741-A9-003), CRUSA-CSIC (project 2007CR0004), Ministerio de Innovación y Ciencia (Madrid, Spain) (grant BFU2007-61563), and the EchiTAb Study Group in partnership with the Federal Ministry of Health, Republic of Nigeria.

Authors' addresses: Juan J. Calvete, Pedro Cid, and Libia Sanz, Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain, E-mails: jcalvete@ibv.csic.es, pcid@ibv.csic.es, and libia.sanz@ibv.csic.es. Álvaro Segura, Mauren Villalta, María Herrera, Guillermo León, and José María Gutiérrez, Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica, E-mails: asegura@icp.ucr.ac.cr, mvillalta@icp.ucr.ac.cr, mariah@icp.ucr.ac.cr, guillermo.leon@ucr.ac.cr, and jose.gutierrez@ucr.ac.cr. Robert Harrison and R. David G. Theakston, Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, UK, E-mails: r.harrison@liverpool.ac.uk and r.d.g.theakston@liverpool.ac.uk. Nandul Durfa and Abdusalami Nasidi, Federal Ministry of Health, Abuja, Nigeria, E-mails: ndurfa2004@yahoo.com.uk and nasidia@hotmail.com. David A. Warrell, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK, E-mail: david.warrell@ndm.ox.ac.uk.

Reprint requests: Juan J. Calvete, Instituto de Biomedicina de Valencia, C.S.I.C., Jaume Roig 11, 46010 Valencia, Spain, Tel: 34-96-339-1778, Fax: 34-96-369-0800, E-mail: jcalvete@ibv.csic.es.

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