A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response...

Autores
Montenegro, Valeria Noely; Jaramillo Ortiz, Jose; Paoletta, Martina; Gravisaco, María José; Del Medico Zajac, Maria Paula; Garanzini, Debora Patricia; Valenzano, Magali Nicole; Calamante, Gabriela; Wilkowsky, Silvina Elizabeth
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In the intraerythrocytic protozoan parasites of the genus Babesia both innate and adaptive immune responses are necessary to confer protection against clinical disease. In particular, the adaptive immune response involves the production of neutralizing antibodies as well as the presentation of parasite antigens to CD4+ T lymphocytes by professional antigen-presenting cells. Therefore, the development of alternative vaccines that replace the use of live attenuated strains should include relevant epitopes targeting both B and T cell responses. The aim of this study was to design new Babesia bigemina immunogens and evaluate the humoral and cellular responses in mice. To achieve this, three B. bigemina recombinant antigens called Apical Membrane Antigen 1 (AMA-1), Rhoptry Associated Protein 1 (RAP-1) and the Thrombospondin Related Anonymous Protein 1 (TRAP-1) were obtained. Besides, two recombinant modified vaccinia virus Ankara vectors coding for chimeric constructs containing bioinformatically predicted B and T cell epitopes from the same three antigens were generated. These immunogens were evaluated in prime-boost heterologous schemes. Among the combinations tested, priming with a cocktail of the three proteins followed by a booster immunization with a mix of both viruses induced the highest activation of IFN-γ+ CD4+ and CD8+ antigen-specific T cell responses. Remarkably, all vaccine schemes containing antigen cocktails also induced antibodies that were capable of neutralizing merozoite invasion of bovine erythrocytes in vitro at a level comparable to an anti B. bigemina hyperimmune bovine serum. Our results offer a new perspective for vaccines against B. bigemina combining bioinformatics predictions and prime-boost immunization regimes for future control measures against bovine babesiosis.
Instituto de Biotecnología
Fil: Montenegro, Valeria Noely. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Montenegro, Valeria Noely. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Jaramillo Ortiz, Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Jaramillo Ortiz, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Paoletta, Martina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Paoletta, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gravisaco, Marí­a José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Gravisaco, Marí­a José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Del Medico Zajac, Maria Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Del Medico Zajac, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garanzini, Debora Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Garanzini, Debora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Valenzano, Magali Nicole. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Valenzano, Magali Nicole. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Calamante, Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Calamante, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wilkowsky, Silvina Elizabeth. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Wilkowsky, Silvina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
Ticks and Tick-borne Diseases 13 (5) : 101991 (Septiembre 2022)
Materia
Babesia bigemina
Proteínas Recombinantes
Inmunización
Anticuerpos
Respuesta Inmunológica
Recombinant Proteins
Immunization
Antibodies
Immune Response
Nivel de accesibilidad
acceso restringido
Condiciones de uso
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/12377
Acceder
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spelling A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response in miceMontenegro, Valeria NoelyJaramillo Ortiz, JosePaoletta, MartinaGravisaco, María JoséDel Medico Zajac, Maria PaulaGaranzini, Debora PatriciaValenzano, Magali NicoleCalamante, GabrielaWilkowsky, Silvina ElizabethBabesia bigeminaProteínas RecombinantesInmunizaciónAnticuerposRespuesta InmunológicaRecombinant ProteinsImmunizationAntibodiesImmune ResponseIn the intraerythrocytic protozoan parasites of the genus Babesia both innate and adaptive immune responses are necessary to confer protection against clinical disease. In particular, the adaptive immune response involves the production of neutralizing antibodies as well as the presentation of parasite antigens to CD4+ T lymphocytes by professional antigen-presenting cells. Therefore, the development of alternative vaccines that replace the use of live attenuated strains should include relevant epitopes targeting both B and T cell responses. The aim of this study was to design new Babesia bigemina immunogens and evaluate the humoral and cellular responses in mice. To achieve this, three B. bigemina recombinant antigens called Apical Membrane Antigen 1 (AMA-1), Rhoptry Associated Protein 1 (RAP-1) and the Thrombospondin Related Anonymous Protein 1 (TRAP-1) were obtained. Besides, two recombinant modified vaccinia virus Ankara vectors coding for chimeric constructs containing bioinformatically predicted B and T cell epitopes from the same three antigens were generated. These immunogens were evaluated in prime-boost heterologous schemes. Among the combinations tested, priming with a cocktail of the three proteins followed by a booster immunization with a mix of both viruses induced the highest activation of IFN-γ+ CD4+ and CD8+ antigen-specific T cell responses. Remarkably, all vaccine schemes containing antigen cocktails also induced antibodies that were capable of neutralizing merozoite invasion of bovine erythrocytes in vitro at a level comparable to an anti B. bigemina hyperimmune bovine serum. Our results offer a new perspective for vaccines against B. bigemina combining bioinformatics predictions and prime-boost immunization regimes for future control measures against bovine babesiosis.Instituto de BiotecnologíaFil: Montenegro, Valeria Noely. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Montenegro, Valeria Noely. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jaramillo Ortiz, Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Jaramillo Ortiz, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paoletta, Martina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Paoletta, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gravisaco, Marí­a José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Gravisaco, Marí­a José. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Del Medico Zajac, Maria Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Del Medico Zajac, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garanzini, Debora Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Garanzini, Debora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valenzano, Magali Nicole. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Valenzano, Magali Nicole. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Calamante, Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Calamante, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wilkowsky, Silvina Elizabeth. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Wilkowsky, Silvina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier2022-07-21T15:52:26Z2022-07-21T15:52:26Z2022-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/12377https://www.sciencedirect.com/science/article/abs/pii/S1877959X220009661877-959Xhttps://doi.org/10.1016/j.ttbdis.2022.101991Ticks and Tick-borne Diseases 13 (5) : 101991 (Septiembre 2022)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repograntAgreement/INTA/2019-PD-E5-I102-001/2019-PD-E5-I102-001/AR./Desarrollo de vacunas y tecnologías para mejorar las estrategias profilácticas y terapéuticas de las enfermedades que afectan la producción animal y la salud públicainfo:eu-repo/semantics/restrictedAccess2025-09-04T09:49:28Zoai:localhost:20.500.12123/12377instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-04 09:49:28.383INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response in mice
title A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response in mice
spellingShingle A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response in mice
Montenegro, Valeria Noely
Babesia bigemina
Proteínas Recombinantes
Inmunización
Anticuerpos
Respuesta Inmunológica
Recombinant Proteins
Immunization
Antibodies
Immune Response
title_short A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response in mice
title_full A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response in mice
title_fullStr A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response in mice
title_full_unstemmed A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response in mice
title_sort A prime-boost combination of a three-protein cocktail and multiepitopic MVA as a vaccine against Babesia bigemina elicits neutralizing antibodies and a Th1 cellular immune response in mice
dc.creator.none.fl_str_mv Montenegro, Valeria Noely
Jaramillo Ortiz, Jose
Paoletta, Martina
Gravisaco, María José
Del Medico Zajac, Maria Paula
Garanzini, Debora Patricia
Valenzano, Magali Nicole
Calamante, Gabriela
Wilkowsky, Silvina Elizabeth
author Montenegro, Valeria Noely
author_facet Montenegro, Valeria Noely
Jaramillo Ortiz, Jose
Paoletta, Martina
Gravisaco, María José
Del Medico Zajac, Maria Paula
Garanzini, Debora Patricia
Valenzano, Magali Nicole
Calamante, Gabriela
Wilkowsky, Silvina Elizabeth
author_role author
author2 Jaramillo Ortiz, Jose
Paoletta, Martina
Gravisaco, María José
Del Medico Zajac, Maria Paula
Garanzini, Debora Patricia
Valenzano, Magali Nicole
Calamante, Gabriela
Wilkowsky, Silvina Elizabeth
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Babesia bigemina
Proteínas Recombinantes
Inmunización
Anticuerpos
Respuesta Inmunológica
Recombinant Proteins
Immunization
Antibodies
Immune Response
topic Babesia bigemina
Proteínas Recombinantes
Inmunización
Anticuerpos
Respuesta Inmunológica
Recombinant Proteins
Immunization
Antibodies
Immune Response
dc.description.none.fl_txt_mv In the intraerythrocytic protozoan parasites of the genus Babesia both innate and adaptive immune responses are necessary to confer protection against clinical disease. In particular, the adaptive immune response involves the production of neutralizing antibodies as well as the presentation of parasite antigens to CD4+ T lymphocytes by professional antigen-presenting cells. Therefore, the development of alternative vaccines that replace the use of live attenuated strains should include relevant epitopes targeting both B and T cell responses. The aim of this study was to design new Babesia bigemina immunogens and evaluate the humoral and cellular responses in mice. To achieve this, three B. bigemina recombinant antigens called Apical Membrane Antigen 1 (AMA-1), Rhoptry Associated Protein 1 (RAP-1) and the Thrombospondin Related Anonymous Protein 1 (TRAP-1) were obtained. Besides, two recombinant modified vaccinia virus Ankara vectors coding for chimeric constructs containing bioinformatically predicted B and T cell epitopes from the same three antigens were generated. These immunogens were evaluated in prime-boost heterologous schemes. Among the combinations tested, priming with a cocktail of the three proteins followed by a booster immunization with a mix of both viruses induced the highest activation of IFN-γ+ CD4+ and CD8+ antigen-specific T cell responses. Remarkably, all vaccine schemes containing antigen cocktails also induced antibodies that were capable of neutralizing merozoite invasion of bovine erythrocytes in vitro at a level comparable to an anti B. bigemina hyperimmune bovine serum. Our results offer a new perspective for vaccines against B. bigemina combining bioinformatics predictions and prime-boost immunization regimes for future control measures against bovine babesiosis.
Instituto de Biotecnología
Fil: Montenegro, Valeria Noely. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Montenegro, Valeria Noely. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Jaramillo Ortiz, Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Jaramillo Ortiz, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Paoletta, Martina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Paoletta, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gravisaco, Marí­a José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Gravisaco, Marí­a José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Del Medico Zajac, Maria Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Del Medico Zajac, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Garanzini, Debora Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Garanzini, Debora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Valenzano, Magali Nicole. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Valenzano, Magali Nicole. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Calamante, Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Calamante, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wilkowsky, Silvina Elizabeth. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Wilkowsky, Silvina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description In the intraerythrocytic protozoan parasites of the genus Babesia both innate and adaptive immune responses are necessary to confer protection against clinical disease. In particular, the adaptive immune response involves the production of neutralizing antibodies as well as the presentation of parasite antigens to CD4+ T lymphocytes by professional antigen-presenting cells. Therefore, the development of alternative vaccines that replace the use of live attenuated strains should include relevant epitopes targeting both B and T cell responses. The aim of this study was to design new Babesia bigemina immunogens and evaluate the humoral and cellular responses in mice. To achieve this, three B. bigemina recombinant antigens called Apical Membrane Antigen 1 (AMA-1), Rhoptry Associated Protein 1 (RAP-1) and the Thrombospondin Related Anonymous Protein 1 (TRAP-1) were obtained. Besides, two recombinant modified vaccinia virus Ankara vectors coding for chimeric constructs containing bioinformatically predicted B and T cell epitopes from the same three antigens were generated. These immunogens were evaluated in prime-boost heterologous schemes. Among the combinations tested, priming with a cocktail of the three proteins followed by a booster immunization with a mix of both viruses induced the highest activation of IFN-γ+ CD4+ and CD8+ antigen-specific T cell responses. Remarkably, all vaccine schemes containing antigen cocktails also induced antibodies that were capable of neutralizing merozoite invasion of bovine erythrocytes in vitro at a level comparable to an anti B. bigemina hyperimmune bovine serum. Our results offer a new perspective for vaccines against B. bigemina combining bioinformatics predictions and prime-boost immunization regimes for future control measures against bovine babesiosis.
publishDate 2022
dc.date.none.fl_str_mv 2022-07-21T15:52:26Z
2022-07-21T15:52:26Z
2022-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/12377
https://www.sciencedirect.com/science/article/abs/pii/S1877959X22000966
1877-959X
https://doi.org/10.1016/j.ttbdis.2022.101991
url http://hdl.handle.net/20.500.12123/12377
https://www.sciencedirect.com/science/article/abs/pii/S1877959X22000966
https://doi.org/10.1016/j.ttbdis.2022.101991
identifier_str_mv 1877-959X
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repograntAgreement/INTA/2019-PD-E5-I102-001/2019-PD-E5-I102-001/AR./Desarrollo de vacunas y tecnologías para mejorar las estrategias profilácticas y terapéuticas de las enfermedades que afectan la producción animal y la salud pública
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
eu_rights_str_mv restrictedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Ticks and Tick-borne Diseases 13 (5) : 101991 (Septiembre 2022)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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