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
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 paras...
| Main Authors: | , , , , , , , , |
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| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
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Elsevier
2022
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| Online Access: | 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 |
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| author | 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_browse | Calamante, Gabriela Del Medico Zajac, Maria Paula Garanzini, Debora Patricia Gravisaco, María José Jaramillo Ortiz, Jose Montenegro, Valeria Noely Paoletta, Martina Valenzano, Magali Nicole Wilkowsky, Silvina Elizabeth |
| 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_sort | Montenegro, Valeria Noely |
| collection | INTA Digital |
| 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. |
| format | info:ar-repo/semantics/artículo |
| id | INTA12377 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | INTA123772022-07-22T14:32:48Z 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 Jaramillo Ortiz, Jose Paoletta, Martina Gravisaco, María José Del Medico Zajac, Maria Paula Garanzini, Debora Patricia Valenzano, Magali Nicole Calamante, Gabriela Wilkowsky, Silvina Elizabeth Babesia bigemina Proteínas Recombinantes Inmunización Anticuerpos Respuesta Inmunológica Recombinant Proteins Immunization Antibodies Immune Response 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 2022-07-21T15:52:26Z 2022-07-21T15:52:26Z 2022-09 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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 info:eu-repo/semantics/restrictedAccess application/pdf Elsevier Ticks and Tick-borne Diseases 13 (5) : 101991 (Septiembre 2022) |
| spellingShingle | Babesia bigemina Proteínas Recombinantes Inmunización Anticuerpos Respuesta Inmunológica Recombinant Proteins Immunization Antibodies Immune Response 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 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 |
| 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_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_sort | 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 |
| topic | Babesia bigemina Proteínas Recombinantes Inmunización Anticuerpos Respuesta Inmunológica Recombinant Proteins Immunization Antibodies Immune Response |
| 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 |
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