Cross-reactivity, antivenomics, and neutralization of toxic activities of Lachesis venoms by polyspecific and monospecific antivenoms

Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against ven...

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Published inPLoS neglected tropical diseases Vol. 11; no. 8; p. e0005793
Main Authors Madrigal, Marvin, Pla, Davinia, Sanz, Libia, Barboza, Elexandra, Arroyo-Portilla, Cynthia, Corrêa-Netto, Carlos, Gutiérrez, José María, Alape-Girón, Alberto, Flores-Díaz, Marietta, Calvete, Juan J.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 01.08.2017
Public Library of Science (PLoS)
Subjects
Antivenins
Antivenins - pharmacology
Antivenom
Biology and Life Sciences
Coagulants
Cross Reactions
Cross-reactivity
Crotalid Venoms - antagonists & inhibitors
Dosage and administration
Epitopes
Equivalence
Funding
Geographical distribution
Hemorrhage
Immunization
Immunologic Factors - pharmacology
Immunoreactivity
Medicine and Health Sciences
Methods
Neutralization
Neutralization Tests
People and places
Phenotypes
Proteolysis
Proteomics
Rattlesnakes
Research and Analysis Methods
Snakes
Species
Studies
Supervision
Taxa
Tropical diseases
Venom
Venoms
South America
Brazil
Costa Rica
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Abstract Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against venom from any of them may exhibit paraspecificity against all the other congeneric taxa. To assess this hypothesis, in this work we have applied antivenomics and immunochemical methods to investigate the immunoreactivity of three monovalent antivenoms and two polyvalent antivenoms towards the venoms from different geographic populations of three different Lachesis species. The ability of the antivenoms to neutralize the proteolytic, hemorrhagic, coagulant, and lethal activities of the seven Lachesis venoms was also investigated. A conspicuous pattern of immunorecognition and cross-neutralization for all effects was evident by the polyspecific antivenoms, indicating large immunoreactive epitope conservation across the genus during more than 10 million years since the Central and South American bushmasters diverged. Despite the broad geographic distribution of Lachesis, antivenoms against venoms of different species are effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that they can be used equivalently for the clinical treatment of any lachesic envenoming. This study demonstrates that antivenoms raised against venom of different Lachesis species are indistinctly effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that antivenoms against conspecific venoms may be used equivalently for the clinical treatment of envenomings caused by any bushmaster species.
AbstractList BackgroundBothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against venom from any of them may exhibit paraspecificity against all the other congeneric taxa.MethodsTo assess this hypothesis, in this work we have applied antivenomics and immunochemical methods to investigate the immunoreactivity of three monovalent antivenoms and two polyvalent antivenoms towards the venoms from different geographic populations of three different Lachesis species. The ability of the antivenoms to neutralize the proteolytic, hemorrhagic, coagulant, and lethal activities of the seven Lachesis venoms was also investigated.ResultsA conspicuous pattern of immunorecognition and cross-neutralization for all effects was evident by the polyspecific antivenoms, indicating large immunoreactive epitope conservation across the genus during more than 10 million years since the Central and South American bushmasters diverged.ConclusionsDespite the broad geographic distribution of Lachesis, antivenoms against venoms of different species are effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that they can be used equivalently for the clinical treatment of any lachesic envenoming.General significanceThis study demonstrates that antivenoms raised against venom of different Lachesis species are indistinctly effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that antivenoms against conspecific venoms may be used equivalently for the clinical treatment of envenomings caused by any bushmaster species.
Snakebite envenoming is a neglected public health problem in many developing countries and antivenom administration constitutes the mainstay in the treatment of such envenomings. Therapeutic antivenoms contain animal-derived antibodies against venom toxins and are produced by immunizing animals with the venom from one or several snake species from a defined geographical area. Defining the geographic boundaries of the efficiency of an antivenom therefore has implications for its rational and efficient use. In Central and South America most accidents are caused by pitvipers of the genus Bothrops , Crotalus and Lachesis . There are four Lachesis species distributed in a variety of habitats ranging from the Caribbean coast of Central America to the Atlantic rainforest of Brazil. Lachesis species cause severe envenomings in humans due to the toxicity of their venoms and also to the large amount of venom they inject into their victims. In this work we investigate the capability of several antivenoms to neutralize the toxic activities of a panel of Lachesis venoms. The results demonstrate that antivenoms raised by immunizing horses with the venoms of different Lachesis species are effective at neutralizing congeneric venoms not used in the immunization, indicating that they could be used equivalently for the clinical treatment of any lachesic envenoming.
Background Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against venom from any of them may exhibit paraspecificity against all the other congeneric taxa. Methods To assess this hypothesis, in this work we have applied antivenomics and immunochemical methods to investigate the immunoreactivity of three monovalent antivenoms and two polyvalent antivenoms towards the venoms from different geographic populations of three different Lachesis species. The ability of the antivenoms to neutralize the proteolytic, hemorrhagic, coagulant, and lethal activities of the seven Lachesis venoms was also investigated. Results A conspicuous pattern of immunorecognition and cross-neutralization for all effects was evident by the polyspecific antivenoms, indicating large immunoreactive epitope conservation across the genus during more than 10 million years since the Central and South American bushmasters diverged. Conclusions Despite the broad geographic distribution of Lachesis, antivenoms against venoms of different species are effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that they can be used equivalently for the clinical treatment of any lachesic envenoming. General significance This study demonstrates that antivenoms raised against venom of different Lachesis species are indistinctly effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that antivenoms against conspecific venoms may be used equivalently for the clinical treatment of envenomings caused by any bushmaster species.
Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against venom from any of them may exhibit paraspecificity against all the other congeneric taxa. To assess this hypothesis, in this work we have applied antivenomics and immunochemical methods to investigate the immunoreactivity of three monovalent antivenoms and two polyvalent antivenoms towards the venoms from different geographic populations of three different Lachesis species. The ability of the antivenoms to neutralize the proteolytic, hemorrhagic, coagulant, and lethal activities of the seven Lachesis venoms was also investigated. A conspicuous pattern of immunorecognition and cross-neutralization for all effects was evident by the polyspecific antivenoms, indicating large immunoreactive epitope conservation across the genus during more than 10 million years since the Central and South American bushmasters diverged. Despite the broad geographic distribution of Lachesis, antivenoms against venoms of different species are effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that they can be used equivalently for the clinical treatment of any lachesic envenoming. This study demonstrates that antivenoms raised against venom of different Lachesis species are indistinctly effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that antivenoms against conspecific venoms may be used equivalently for the clinical treatment of envenomings caused by any bushmaster species.
Background Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against venom from any of them may exhibit paraspecificity against all the other congeneric taxa. Methods To assess this hypothesis, in this work we have applied antivenomics and immunochemical methods to investigate the immunoreactivity of three monovalent antivenoms and two polyvalent antivenoms towards the venoms from different geographic populations of three different Lachesis species. The ability of the antivenoms to neutralize the proteolytic, hemorrhagic, coagulant, and lethal activities of the seven Lachesis venoms was also investigated. Results A conspicuous pattern of immunorecognition and cross-neutralization for all effects was evident by the polyspecific antivenoms, indicating large immunoreactive epitope conservation across the genus during more than 10 million years since the Central and South American bushmasters diverged. Conclusions Despite the broad geographic distribution of Lachesis, antivenoms against venoms of different species are effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that they can be used equivalently for the clinical treatment of any lachesic envenoming. General significance This study demonstrates that antivenoms raised against venom of different Lachesis species are indistinctly effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that antivenoms against conspecific venoms may be used equivalently for the clinical treatment of envenomings caused by any bushmaster species.
Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against venom from any of them may exhibit paraspecificity against all the other congeneric taxa.BACKGROUNDBothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against venom from any of them may exhibit paraspecificity against all the other congeneric taxa.To assess this hypothesis, in this work we have applied antivenomics and immunochemical methods to investigate the immunoreactivity of three monovalent antivenoms and two polyvalent antivenoms towards the venoms from different geographic populations of three different Lachesis species. The ability of the antivenoms to neutralize the proteolytic, hemorrhagic, coagulant, and lethal activities of the seven Lachesis venoms was also investigated.METHODSTo assess this hypothesis, in this work we have applied antivenomics and immunochemical methods to investigate the immunoreactivity of three monovalent antivenoms and two polyvalent antivenoms towards the venoms from different geographic populations of three different Lachesis species. The ability of the antivenoms to neutralize the proteolytic, hemorrhagic, coagulant, and lethal activities of the seven Lachesis venoms was also investigated.A conspicuous pattern of immunorecognition and cross-neutralization for all effects was evident by the polyspecific antivenoms, indicating large immunoreactive epitope conservation across the genus during more than 10 million years since the Central and South American bushmasters diverged.RESULTSA conspicuous pattern of immunorecognition and cross-neutralization for all effects was evident by the polyspecific antivenoms, indicating large immunoreactive epitope conservation across the genus during more than 10 million years since the Central and South American bushmasters diverged.Despite the broad geographic distribution of Lachesis, antivenoms against venoms of different species are effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that they can be used equivalently for the clinical treatment of any lachesic envenoming.CONCLUSIONSDespite the broad geographic distribution of Lachesis, antivenoms against venoms of different species are effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that they can be used equivalently for the clinical treatment of any lachesic envenoming.This study demonstrates that antivenoms raised against venom of different Lachesis species are indistinctly effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that antivenoms against conspecific venoms may be used equivalently for the clinical treatment of envenomings caused by any bushmaster species.GENERAL SIGNIFICANCEThis study demonstrates that antivenoms raised against venom of different Lachesis species are indistinctly effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that antivenoms against conspecific venoms may be used equivalently for the clinical treatment of envenomings caused by any bushmaster species.
Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against venom from any of them may exhibit paraspecificity against all the other congeneric taxa. To assess this hypothesis, in this work we have applied antivenomics and immunochemical methods to investigate the immunoreactivity of three monovalent antivenoms and two polyvalent antivenoms towards the venoms from different geographic populations of three different Lachesis species. The ability of the antivenoms to neutralize the proteolytic, hemorrhagic, coagulant, and lethal activities of the seven Lachesis venoms was also investigated. A conspicuous pattern of immunorecognition and cross-neutralization for all effects was evident by the polyspecific antivenoms, indicating large immunoreactive epitope conservation across the genus during more than 10 million years since the Central and South American bushmasters diverged. Despite the broad geographic distribution of Lachesis, antivenoms against venoms of different species are effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that they can be used equivalently for the clinical treatment of any lachesic envenoming.
Audience Academic
Author Corrêa-Netto, Carlos
Sanz, Libia
Arroyo-Portilla, Cynthia
Madrigal, Marvin
Pla, Davinia
Flores-Díaz, Marietta
Calvete, Juan J.
Barboza, Elexandra
Gutiérrez, José María
Alape-Girón, Alberto
AuthorAffiliation Liverpool School of Tropical Medicine, UNITED KINGDOM
2 Departamento de Bioquímica, Facultad de Medicina, Universidad de Costa Rica, San José, Costa Rica
3 Laboratorio de Venómica Estructural y Funcional, Instituto de Biomedicina de Valencia, C.S.I.C., Valencia, Spain
1 Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica
4 Instituto Vital Brazil, Niterói, Rio de Janeiro, Brazil
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/28787445$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright COPYRIGHT 2017 Public Library of Science
2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: venoms by polyspecific and monospecific antivenoms. PLoS Negl Trop Dis 11(8): e0005793. https://doi.org/10.1371/journal.pntd.0005793
2017 Madrigal et al 2017 Madrigal et al
2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: venoms by polyspecific and monospecific antivenoms. PLoS Negl Trop Dis 11(8): e0005793. https://doi.org/10.1371/journal.pntd.0005793
Copyright_xml – notice: COPYRIGHT 2017 Public Library of Science
– notice: 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: venoms by polyspecific and monospecific antivenoms. PLoS Negl Trop Dis 11(8): e0005793. https://doi.org/10.1371/journal.pntd.0005793
– notice: 2017 Madrigal et al 2017 Madrigal et al
– notice: 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: venoms by polyspecific and monospecific antivenoms. PLoS Negl Trop Dis 11(8): e0005793. https://doi.org/10.1371/journal.pntd.0005793
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Snippet Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and...
Background Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom...
Snakebite envenoming is a neglected public health problem in many developing countries and antivenom administration constitutes the mainstay in the treatment...
BackgroundBothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype...
Background Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom...
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StartPage e0005793
SubjectTerms Antivenins
Antivenins - pharmacology
Antivenom
Biology and Life Sciences
Coagulants
Cross Reactions
Cross-reactivity
Crotalid Venoms - antagonists & inhibitors
Dosage and administration
Epitopes
Equivalence
Funding
Geographical distribution
Hemorrhage
Immunization
Immunologic Factors - pharmacology
Immunoreactivity
Medicine and Health Sciences
Methods
Neutralization
Neutralization Tests
People and places
Phenotypes
Proteolysis
Proteomics
Rattlesnakes
Research and Analysis Methods
Snakes
Species
Studies
Supervision
Taxa
Tropical diseases
Venom
Venoms
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Title Cross-reactivity, antivenomics, and neutralization of toxic activities of Lachesis venoms by polyspecific and monospecific antivenoms
URI https://www.ncbi.nlm.nih.gov/pubmed/28787445
https://www.proquest.com/docview/1939438755
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http://dx.doi.org/10.1371/journal.pntd.0005793
Volume 11
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