Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/49776 |
Resumo: | Department of Proteomics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba. |
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González, Luis JavierGuzmán, Pedro E. EncinosaMachado, WendyPousa, SatomyLeyva, AlejandroArguelles, Ana Laura CanoCabrera, GleysinEspinosa, Luis ArielParra, RubénHernández, RachelSoto, Yamil BelloLedesma, Frank L.Joglar, MarisdaniaGuirola, OsmanyKurt, Louise UlrichCarvalho, Paulo CostaCabrales, AniaGaray, HildaBesada, VladimirDurán, RosarioTakao, ToshifumiEstrada, Mario PabloRodríguez-Mallon, Alina2021-11-11T15:18:57Z2021-11-11T15:18:57Z2021GONZÁLEZ, Luis Javier. et al. Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis. Analytical and Bioanalytical Chemistry, p. 1–16, 2021.1618-2650https://www.arca.fiocruz.br/handle/icict/4977610.1007/s00216-021-03569-0porSpringerMegathura Crenulatap64KTick InfestationsVaccinesP0 ProteinHemocyaninsPeptidesMass SpectrometryInfestaciones por GarrapatasVacunasProteína P0HemocianinasPéptidosEspectrometría de MasasInfestations par les tiquesVaccinsProtéine P0HémocyaninePeptidesSpectrométrie de masseInfestações por CarrapatoVacinasProteína P0HemocianinasPeptídeosEspectrometria de MassasSynthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleDepartment of Proteomics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Animal Biotechnology Department. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Department of Proteomics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Department of Proteomics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Institut Pasteur de Montevideo. Unidad de Bioquímica y Proteómica Analítica. Montevideo, Uruguay. / Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.Animal Biotechnology Department. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Department of Proteomics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Department of Proteomics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Department of Proteomics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Department of Proteomics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Animal Biotechnology Department. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Animal Biotechnology Department. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Animal Biotechnology Department. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Bioinformatics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.Synthetic Peptides Laboratory. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Synthetic Peptides Laboratory. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Department of Proteomics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Institut Pasteur de Montevideo. Unidad de Bioquímica y Proteómica Analítica. Montevideo, Uruguay. / Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.Institute for Protein Research. Osaka University. Osaka, Japan.Animal Biotechnology Department. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.Animal Biotechnology Department. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba.A peptide from the P0 acidic ribosomal protein (pP0) of ticks conjugated to keyhole limpet hemocyanin from Megathura crenulata has shown to be effective against different tick species when used in host vaccination. Turning this peptide into a commercial anti-tick vaccine will depend on finding the appropriate, technically and economically feasible way to present it to the host immune system. Two conjugates (p64K-Cys1pP0 and p64K-βAla1pP0) were synthesized using the p64K carrier protein from Neisseria meningitidis produced in Escherichia coli, the same cross-linking reagent, and two analogues of pP0. The SDS-PAGE analysis of p64K-Cys1pP0 showed a heterogeneous conjugate compared to p64K-βAla1pP0 that was detected as a protein band at 91kDa. The pP0/p64K ratio determined by MALDI-MS for p64K-Cys1pP0 ranged from 1 to 8, being 3-5 the predominant ratio, while in the case of p64K-βAla1pP0 this ratio was 5-7. Cys1pP0 was partially linked to 35 out of 39 Lys residues and the N-terminal end, while βAla1pP0 was mostly linked to the six free cysteine residues, to the N-terminal end, and, in a lesser extent, to Lys residues. The assignment of the conjugation sites and side reactions were based on the identification of type 2 peptides. Rabbit immunizations showed the best anti-pP0 titers and the highest efficacy against Rhipicephalus sanguineus ticks when the p64K-Cys1pP0 was used as vaccine antigen. The presence of high molecular mass aggregates observed in the SDS-PAGE analysis of p64K-Cys1pP0 could be responsible for a better immune response against pP0 and consequently for its better efficacy as an anti-tick vaccine. Graphical abstract.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83084https://www.arca.fiocruz.br/bitstream/icict/49776/1/license.txt783568c2893d2e25a99990b126be1772MD51ORIGINALGonzález2021_Article_SynthesisLC-ok.pdfGonzález2021_Article_SynthesisLC-ok.pdfapplication/pdf2248298https://www.arca.fiocruz.br/bitstream/icict/49776/2/Gonz%c3%a1lez2021_Article_SynthesisLC-ok.pdff5a0096b9ee7ac8b7f1bda1d8c4d0989MD52icict/497762021-11-11 12:18:57.355oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352021-11-11T15:18:57Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.pt_BR.fl_str_mv |
Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis |
title |
Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis |
spellingShingle |
Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis González, Luis Javier Megathura Crenulata p64K Tick Infestations Vaccines P0 Protein Hemocyanins Peptides Mass Spectrometry Infestaciones por Garrapatas Vacunas Proteína P0 Hemocianinas Péptidos Espectrometría de Masas Infestations par les tiques Vaccins Protéine P0 Hémocyanine Peptides Spectrométrie de masse Infestações por Carrapato Vacinas Proteína P0 Hemocianinas Peptídeos Espectrometria de Massas |
title_short |
Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis |
title_full |
Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis |
title_fullStr |
Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis |
title_full_unstemmed |
Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis |
title_sort |
Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis |
author |
González, Luis Javier |
author_facet |
González, Luis Javier Guzmán, Pedro E. Encinosa Machado, Wendy Pousa, Satomy Leyva, Alejandro Arguelles, Ana Laura Cano Cabrera, Gleysin Espinosa, Luis Ariel Parra, Rubén Hernández, Rachel Soto, Yamil Bello Ledesma, Frank L. Joglar, Marisdania Guirola, Osmany Kurt, Louise Ulrich Carvalho, Paulo Costa Cabrales, Ania Garay, Hilda Besada, Vladimir Durán, Rosario Takao, Toshifumi Estrada, Mario Pablo Rodríguez-Mallon, Alina |
author_role |
author |
author2 |
Guzmán, Pedro E. Encinosa Machado, Wendy Pousa, Satomy Leyva, Alejandro Arguelles, Ana Laura Cano Cabrera, Gleysin Espinosa, Luis Ariel Parra, Rubén Hernández, Rachel Soto, Yamil Bello Ledesma, Frank L. Joglar, Marisdania Guirola, Osmany Kurt, Louise Ulrich Carvalho, Paulo Costa Cabrales, Ania Garay, Hilda Besada, Vladimir Durán, Rosario Takao, Toshifumi Estrada, Mario Pablo Rodríguez-Mallon, Alina |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
González, Luis Javier Guzmán, Pedro E. Encinosa Machado, Wendy Pousa, Satomy Leyva, Alejandro Arguelles, Ana Laura Cano Cabrera, Gleysin Espinosa, Luis Ariel Parra, Rubén Hernández, Rachel Soto, Yamil Bello Ledesma, Frank L. Joglar, Marisdania Guirola, Osmany Kurt, Louise Ulrich Carvalho, Paulo Costa Cabrales, Ania Garay, Hilda Besada, Vladimir Durán, Rosario Takao, Toshifumi Estrada, Mario Pablo Rodríguez-Mallon, Alina |
dc.subject.other.pt_BR.fl_str_mv |
Megathura Crenulata p64K |
topic |
Megathura Crenulata p64K Tick Infestations Vaccines P0 Protein Hemocyanins Peptides Mass Spectrometry Infestaciones por Garrapatas Vacunas Proteína P0 Hemocianinas Péptidos Espectrometría de Masas Infestations par les tiques Vaccins Protéine P0 Hémocyanine Peptides Spectrométrie de masse Infestações por Carrapato Vacinas Proteína P0 Hemocianinas Peptídeos Espectrometria de Massas |
dc.subject.en.pt_BR.fl_str_mv |
Tick Infestations Vaccines P0 Protein Hemocyanins Peptides Mass Spectrometry |
dc.subject.es.pt_BR.fl_str_mv |
Infestaciones por Garrapatas Vacunas Proteína P0 Hemocianinas Péptidos Espectrometría de Masas |
dc.subject.fr.pt_BR.fl_str_mv |
Infestations par les tiques Vaccins Protéine P0 Hémocyanine Peptides Spectrométrie de masse |
dc.subject.decs.pt_BR.fl_str_mv |
Infestações por Carrapato Vacinas Proteína P0 Hemocianinas Peptídeos Espectrometria de Massas |
description |
Department of Proteomics. Center for Genetic Engineering and Biotechnology. Cubanacán, Havana, Cuba. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-11-11T15:18:57Z |
dc.date.available.fl_str_mv |
2021-11-11T15:18:57Z |
dc.date.issued.fl_str_mv |
2021 |
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.citation.fl_str_mv |
GONZÁLEZ, Luis Javier. et al. Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis. Analytical and Bioanalytical Chemistry, p. 1–16, 2021. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/49776 |
dc.identifier.issn.pt_BR.fl_str_mv |
1618-2650 |
dc.identifier.doi.none.fl_str_mv |
10.1007/s00216-021-03569-0 |
identifier_str_mv |
GONZÁLEZ, Luis Javier. et al. Synthesis, LC-MS/MS analysis, and biological evaluation of two vaccine candidates against ticks based on the antigenic P0 peptide from R. sanguineus linked to the p64K carrier protein from Neisseria meningitidis. Analytical and Bioanalytical Chemistry, p. 1–16, 2021. 1618-2650 10.1007/s00216-021-03569-0 |
url |
https://www.arca.fiocruz.br/handle/icict/49776 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
Springer |
publisher.none.fl_str_mv |
Springer |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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