A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigens

Detalhes bibliográficos
Autor(a) principal: Polli, Nayanne Louise Costacurta
Data de Publicação: 2021
Outros Autores: Justa, Hanna Camara da, Antunes, Bruno Cesar, Silva, Thais Pereira da, Dittrich, Rosangela Locatelli, de Souza, Giovana Scuissiatto, Wille, Ana Carolina Martins, Matsubara, Fernando Hitomi, Minozzo, João Carlos [UNESP], Mariutti, Ricardo Barros [UNESP], Arni, Raghuvir Krishnaswamy [UNESP], Senff-Ribeiro, Andrea, Veiga, Silvio Sanches, Gremski, Luiza Helena
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.ijbiomac.2021.10.005
http://hdl.handle.net/11449/233692
Resumo: Accidents involving Brown spiders are reported throughout the world. In the venom, the major toxins involved in the deleterious effects are phospholipases D (PLDs). In this work, recombinant mutated phospholipases D from three endemic species medically relevant in South America (Loxosceles intermedia, L. laeta and L. gaucho) were tested as antigens in a vaccination protocol. In such isoforms, key amino acid residues involved in catalysis, magnesium-ion coordination, and binding to substrates were replaced by Alanine (H12A-H47A, E32A-D34A and W230A). These mutations eliminated the phospholipase activity and reduced the generation of skin necrosis and edema to residual levels. Molecular modeling of mutated isoforms indicated that the three-dimensional structures, topologies, and surface charges did not undergo significant changes. Mutated isoforms were recognized by sera against the crude venoms. Vaccination protocols in rabbits using mutated isoforms generated a serum that recognized the native PLDs of crude venoms and neutralized dermonecrosis and edema induced by L. intermedia venom. Vaccination of mice prevented the lethal effects of L. intermedia crude venom. Furthermore, vaccination of rabbits prevented the cutaneous lesion triggered by the three venoms. These results indicate a great potential for mutated recombinant PLDs to be employed as antigens in developing protective vaccines for Loxoscelism.
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spelling A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigensBrown spiderLoxoscelismMutated phospholipases DVaccinesAccidents involving Brown spiders are reported throughout the world. In the venom, the major toxins involved in the deleterious effects are phospholipases D (PLDs). In this work, recombinant mutated phospholipases D from three endemic species medically relevant in South America (Loxosceles intermedia, L. laeta and L. gaucho) were tested as antigens in a vaccination protocol. In such isoforms, key amino acid residues involved in catalysis, magnesium-ion coordination, and binding to substrates were replaced by Alanine (H12A-H47A, E32A-D34A and W230A). These mutations eliminated the phospholipase activity and reduced the generation of skin necrosis and edema to residual levels. Molecular modeling of mutated isoforms indicated that the three-dimensional structures, topologies, and surface charges did not undergo significant changes. Mutated isoforms were recognized by sera against the crude venoms. Vaccination protocols in rabbits using mutated isoforms generated a serum that recognized the native PLDs of crude venoms and neutralized dermonecrosis and edema induced by L. intermedia venom. Vaccination of mice prevented the lethal effects of L. intermedia crude venom. Furthermore, vaccination of rabbits prevented the cutaneous lesion triggered by the three venoms. These results indicate a great potential for mutated recombinant PLDs to be employed as antigens in developing protective vaccines for Loxoscelism.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal do ParanáFundação AraucáriaConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Cell Biology Federal University of Paraná (UFPR)Production and Research Center of Immunobiological Products (CPPI) State Department of HealthVeterinary Hospital Federal University of Paraná (UFPR)Department of Structural Molecular Biology and Genetics State University of Ponta Grossa (UEPG)Multiuser Center for Biomolecular Innovation Departament of Physics Universidade Estadual Paulista (UNESP)Multiuser Center for Biomolecular Innovation Departament of Physics Universidade Estadual Paulista (UNESP)Universidade Federal do Paraná: 02/2020Universidade Federal do Paraná: 04/2019Fundação Araucária: 057/2017CNPq: 303868/2016-3CNPq: 408633/2018-2Universidade Federal do Paraná (UFPR)State Department of HealthUniversidade Estadual de Ponta Grossa (UEPG)Universidade Estadual Paulista (UNESP)Polli, Nayanne Louise CostacurtaJusta, Hanna Camara daAntunes, Bruno CesarSilva, Thais Pereira daDittrich, Rosangela Locatellide Souza, Giovana ScuissiattoWille, Ana Carolina MartinsMatsubara, Fernando HitomiMinozzo, João Carlos [UNESP]Mariutti, Ricardo Barros [UNESP]Arni, Raghuvir Krishnaswamy [UNESP]Senff-Ribeiro, AndreaVeiga, Silvio SanchesGremski, Luiza Helena2022-05-01T09:47:17Z2022-05-01T09:47:17Z2021-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article757-770http://dx.doi.org/10.1016/j.ijbiomac.2021.10.005International Journal of Biological Macromolecules, v. 192, p. 757-770.1879-00030141-8130http://hdl.handle.net/11449/23369210.1016/j.ijbiomac.2021.10.0052-s2.0-85117249680Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Biological Macromoleculesinfo:eu-repo/semantics/openAccess2022-05-01T09:47:17Zoai:repositorio.unesp.br:11449/233692Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:56:02.826290Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigens
title A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigens
spellingShingle A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigens
Polli, Nayanne Louise Costacurta
Brown spider
Loxoscelism
Mutated phospholipases D
Vaccines
title_short A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigens
title_full A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigens
title_fullStr A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigens
title_full_unstemmed A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigens
title_sort A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigens
author Polli, Nayanne Louise Costacurta
author_facet Polli, Nayanne Louise Costacurta
Justa, Hanna Camara da
Antunes, Bruno Cesar
Silva, Thais Pereira da
Dittrich, Rosangela Locatelli
de Souza, Giovana Scuissiatto
Wille, Ana Carolina Martins
Matsubara, Fernando Hitomi
Minozzo, João Carlos [UNESP]
Mariutti, Ricardo Barros [UNESP]
Arni, Raghuvir Krishnaswamy [UNESP]
Senff-Ribeiro, Andrea
Veiga, Silvio Sanches
Gremski, Luiza Helena
author_role author
author2 Justa, Hanna Camara da
Antunes, Bruno Cesar
Silva, Thais Pereira da
Dittrich, Rosangela Locatelli
de Souza, Giovana Scuissiatto
Wille, Ana Carolina Martins
Matsubara, Fernando Hitomi
Minozzo, João Carlos [UNESP]
Mariutti, Ricardo Barros [UNESP]
Arni, Raghuvir Krishnaswamy [UNESP]
Senff-Ribeiro, Andrea
Veiga, Silvio Sanches
Gremski, Luiza Helena
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal do Paraná (UFPR)
State Department of Health
Universidade Estadual de Ponta Grossa (UEPG)
Universidade Estadual Paulista (UNESP)
dc.contributor.author.fl_str_mv Polli, Nayanne Louise Costacurta
Justa, Hanna Camara da
Antunes, Bruno Cesar
Silva, Thais Pereira da
Dittrich, Rosangela Locatelli
de Souza, Giovana Scuissiatto
Wille, Ana Carolina Martins
Matsubara, Fernando Hitomi
Minozzo, João Carlos [UNESP]
Mariutti, Ricardo Barros [UNESP]
Arni, Raghuvir Krishnaswamy [UNESP]
Senff-Ribeiro, Andrea
Veiga, Silvio Sanches
Gremski, Luiza Helena
dc.subject.por.fl_str_mv Brown spider
Loxoscelism
Mutated phospholipases D
Vaccines
topic Brown spider
Loxoscelism
Mutated phospholipases D
Vaccines
description Accidents involving Brown spiders are reported throughout the world. In the venom, the major toxins involved in the deleterious effects are phospholipases D (PLDs). In this work, recombinant mutated phospholipases D from three endemic species medically relevant in South America (Loxosceles intermedia, L. laeta and L. gaucho) were tested as antigens in a vaccination protocol. In such isoforms, key amino acid residues involved in catalysis, magnesium-ion coordination, and binding to substrates were replaced by Alanine (H12A-H47A, E32A-D34A and W230A). These mutations eliminated the phospholipase activity and reduced the generation of skin necrosis and edema to residual levels. Molecular modeling of mutated isoforms indicated that the three-dimensional structures, topologies, and surface charges did not undergo significant changes. Mutated isoforms were recognized by sera against the crude venoms. Vaccination protocols in rabbits using mutated isoforms generated a serum that recognized the native PLDs of crude venoms and neutralized dermonecrosis and edema induced by L. intermedia venom. Vaccination of mice prevented the lethal effects of L. intermedia crude venom. Furthermore, vaccination of rabbits prevented the cutaneous lesion triggered by the three venoms. These results indicate a great potential for mutated recombinant PLDs to be employed as antigens in developing protective vaccines for Loxoscelism.
publishDate 2021
dc.date.none.fl_str_mv 2021-12-01
2022-05-01T09:47:17Z
2022-05-01T09:47:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.ijbiomac.2021.10.005
International Journal of Biological Macromolecules, v. 192, p. 757-770.
1879-0003
0141-8130
http://hdl.handle.net/11449/233692
10.1016/j.ijbiomac.2021.10.005
2-s2.0-85117249680
url http://dx.doi.org/10.1016/j.ijbiomac.2021.10.005
http://hdl.handle.net/11449/233692
identifier_str_mv International Journal of Biological Macromolecules, v. 192, p. 757-770.
1879-0003
0141-8130
10.1016/j.ijbiomac.2021.10.005
2-s2.0-85117249680
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv International Journal of Biological Macromolecules
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 757-770
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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