A protective vaccine against the toxic activities following Brown spider accidents based on recombinant mutated phospholipases D as antigens
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , |
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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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 |
|
_version_ |
1808129474686877696 |