Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection

Protection against the intraerythrocytic protozoan parasite Babesia bovis depends on both strong innate and adaptive immune response, this latter involving the presentation of parasite antigens to CD4+ T-lymphocytes by professional antigen-presenting cells. Secretion of Th1 cytokines by CD4+ T cell...

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Main Authors: Jaramillo Ortiz, Jose Manuel, Paoletta, Martina, Gravisaco, María José, Lopez Arias, Ludmila Sol, Montenegro, Valeria Noely, De La Fourniere, Sofia, Valenzano, Magali Nicole, Guillemi, Eliana Carolina, Valentini, Beatriz Susana, Echaide, Ignacio Eduardo, Farber, Marisa Diana, Wilkowsky, Silvina Elizabeth
Format: info:ar-repo/semantics/artículo
Language:Inglés
Published: Elsevier 2020
Subjects:
Online Access:http://hdl.handle.net/20.500.12123/6630
https://www.sciencedirect.com/science/article/pii/S1877959X19300901?via%3Dihub
https://doi.org/10.1016/j.ttbdis.2019.101270
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author Jaramillo Ortiz, Jose Manuel
Paoletta, Martina
Gravisaco, María José
Lopez Arias, Ludmila Sol
Montenegro, Valeria Noely
De La Fourniere, Sofia
Valenzano, Magali Nicole
Guillemi, Eliana Carolina
Valentini, Beatriz Susana
Echaide, Ignacio Eduardo
Farber, Marisa Diana
Wilkowsky, Silvina Elizabeth
author_browse De La Fourniere, Sofia
Echaide, Ignacio Eduardo
Farber, Marisa Diana
Gravisaco, María José
Guillemi, Eliana Carolina
Jaramillo Ortiz, Jose Manuel
Lopez Arias, Ludmila Sol
Montenegro, Valeria Noely
Paoletta, Martina
Valentini, Beatriz Susana
Valenzano, Magali Nicole
Wilkowsky, Silvina Elizabeth
author_facet Jaramillo Ortiz, Jose Manuel
Paoletta, Martina
Gravisaco, María José
Lopez Arias, Ludmila Sol
Montenegro, Valeria Noely
De La Fourniere, Sofia
Valenzano, Magali Nicole
Guillemi, Eliana Carolina
Valentini, Beatriz Susana
Echaide, Ignacio Eduardo
Farber, Marisa Diana
Wilkowsky, Silvina Elizabeth
author_sort Jaramillo Ortiz, Jose Manuel
collection INTA Digital
description Protection against the intraerythrocytic protozoan parasite Babesia bovis depends on both strong innate and adaptive immune response, this latter involving the presentation of parasite antigens to CD4+ T-lymphocytes by professional antigen-presenting cells. Secretion of Th1 cytokines by CD4+ T cell is also very important for isotype switching to IgG2, the best opsonising antibody isotype in cattle, to target extracellular parasites and parasite antigens displayed at the erythrocyte surface. In the field of vaccinology, heterologous prime-boost schemes combining protein-adjuvant formulations with a modified vaccinia Ankara vector expressing the same antigen have demonstrated the induction of both humoral and cellular immune responses. It has been previously demonstrated that MVA-infected dendritic cells can present antigens in the context of MHC II and activate CD4+ T cell. These results support the use of the MVA viral vector for a pathogen like Babesia bovis, which only resides within erythrocytes. In this study, 13-15-months-old Holstein-Friesian steers were immunised with a subunit vaccine as a prime and a modified vaccinia Ankara vector as a boost, both expressing a chimeric multi-antigen (rMABbo - rMVA). This antigen includes the immunodominant B and T cell epitopes of three B. bovis proteins: merozoite surface antigen - 2c (MSA - 2c), rhoptry associated protein 1 (RAP - 1) and heat shock protein 20 (HSP20). Responses were compared with the Babesia bovis live attenuated vaccine used in Argentina (R1A). Eleven weeks after the first immunisation, all bovines were challenged by the inoculation of a virulent B. bovis strain. All groups were monitored daily for hyperthermia and reduction of packed cell volume. Both the rMABbo - rMVA and R1A vaccinated animals developed high titters of total IgG antibodies and an antigen-specific Th1 cellular response before and after challenge. However, all rMABbo - rMVA steers showed clinical signs of disease upon challenge. Only the R1A live vaccine group developed an immune response associated with in vitro neutralising antibodies at a level that significantly inhibited the parasite invasion. The lack of protection observed with this recombinant formulation indicates the need to perform further basic and clinical studies in the bovine model in order to achieve the desired effectiveness. This is the first report in which a novel vaccine candidate against Babesia bovis was constructed based on a recombinant and rationally designed viral vector and evaluated in the biological model of the disease.
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spelling INTA66302021-12-28T12:02:39Z Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection Jaramillo Ortiz, Jose Manuel Paoletta, Martina Gravisaco, María José Lopez Arias, Ludmila Sol Montenegro, Valeria Noely De La Fourniere, Sofia Valenzano, Magali Nicole Guillemi, Eliana Carolina Valentini, Beatriz Susana Echaide, Ignacio Eduardo Farber, Marisa Diana Wilkowsky, Silvina Elizabeth Babesia bovis Antígenos Anticuerpos Antigens Antibodies Protection against the intraerythrocytic protozoan parasite Babesia bovis depends on both strong innate and adaptive immune response, this latter involving the presentation of parasite antigens to CD4+ T-lymphocytes by professional antigen-presenting cells. Secretion of Th1 cytokines by CD4+ T cell is also very important for isotype switching to IgG2, the best opsonising antibody isotype in cattle, to target extracellular parasites and parasite antigens displayed at the erythrocyte surface. In the field of vaccinology, heterologous prime-boost schemes combining protein-adjuvant formulations with a modified vaccinia Ankara vector expressing the same antigen have demonstrated the induction of both humoral and cellular immune responses. It has been previously demonstrated that MVA-infected dendritic cells can present antigens in the context of MHC II and activate CD4+ T cell. These results support the use of the MVA viral vector for a pathogen like Babesia bovis, which only resides within erythrocytes. In this study, 13-15-months-old Holstein-Friesian steers were immunised with a subunit vaccine as a prime and a modified vaccinia Ankara vector as a boost, both expressing a chimeric multi-antigen (rMABbo - rMVA). This antigen includes the immunodominant B and T cell epitopes of three B. bovis proteins: merozoite surface antigen - 2c (MSA - 2c), rhoptry associated protein 1 (RAP - 1) and heat shock protein 20 (HSP20). Responses were compared with the Babesia bovis live attenuated vaccine used in Argentina (R1A). Eleven weeks after the first immunisation, all bovines were challenged by the inoculation of a virulent B. bovis strain. All groups were monitored daily for hyperthermia and reduction of packed cell volume. Both the rMABbo - rMVA and R1A vaccinated animals developed high titters of total IgG antibodies and an antigen-specific Th1 cellular response before and after challenge. However, all rMABbo - rMVA steers showed clinical signs of disease upon challenge. Only the R1A live vaccine group developed an immune response associated with in vitro neutralising antibodies at a level that significantly inhibited the parasite invasion. The lack of protection observed with this recombinant formulation indicates the need to perform further basic and clinical studies in the bovine model in order to achieve the desired effectiveness. This is the first report in which a novel vaccine candidate against Babesia bovis was constructed based on a recombinant and rationally designed viral vector and evaluated in the biological model of the disease. Instituto de Biotecnología Fil: Jaramillo Ortiz, Jose Manuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología. Laboratorio de Hemoparásitos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Paoletta, Martina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología. Laboratorio de Hemoparásitos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gravisaco, Marí­a José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología. Laboratorio de Hemoparásitos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Lopez Arias, Ludmila Sol. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología. Laboratorio de Hemoparásitos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Montenegro, Valeria Noely. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología. Laboratorio de Hemoparásitos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: De La Fourniere, Sofia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología. Laboratorio de Hemoparásitos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Valenzano, Magalí Nicole. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología. Laboratorio de Hemoparásitos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Guillemi, Eliana Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología. Laboratorio de Hemoparásitos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Valentini, Beatriz Susana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; Argentina Fil: Echaide, Ignacio Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; Argentina Fil: Farber, Marisa Diana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología. Laboratorio de Hemoparásitos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Wilkowsky, Silvina Elizabeth. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología. Laboratorio de Hemoparásitos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 2020-01-07T17:37:03Z 2020-01-07T17:37:03Z 2019-10 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/6630 https://www.sciencedirect.com/science/article/pii/S1877959X19300901?via%3Dihub 1877-959X https://doi.org/10.1016/j.ttbdis.2019.101270 eng info:eu-repo/semantics/restrictedAccess application/pdf Elsevier Ticks and tick-borne diseases 10 (6) : 101270. (Octubre 2019)
spellingShingle Babesia bovis
Antígenos
Anticuerpos
Antigens
Antibodies
Jaramillo Ortiz, Jose Manuel
Paoletta, Martina
Gravisaco, María José
Lopez Arias, Ludmila Sol
Montenegro, Valeria Noely
De La Fourniere, Sofia
Valenzano, Magali Nicole
Guillemi, Eliana Carolina
Valentini, Beatriz Susana
Echaide, Ignacio Eduardo
Farber, Marisa Diana
Wilkowsky, Silvina Elizabeth
Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection
title Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection
title_full Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection
title_fullStr Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection
title_full_unstemmed Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection
title_short Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection
title_sort immunisation of cattle against babesia bovis combining a multi epitope modified vaccinia ankara virus and a recombinant protein induce strong th1 cell responses but fails to trigger neutralising antibodies required for protection
topic Babesia bovis
Antígenos
Anticuerpos
Antigens
Antibodies
url http://hdl.handle.net/20.500.12123/6630
https://www.sciencedirect.com/science/article/pii/S1877959X19300901?via%3Dihub
https://doi.org/10.1016/j.ttbdis.2019.101270
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