ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease
Abstract Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric pr...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00676-0 |
| _version_ | 1797425438750932992 |
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| author | Julia T. Castro Rory Brito Natalia S. Hojo-Souza Bárbara Azevedo Natalia Salazar Camila P. Ferreira Caroline Junqueira Ana Paula Fernandes Ronnie Vasconcellos Jamille M. Cardoso Rodrigo D. O. Aguiar-Soares Paula M. A. Vieira Cláudia M. Carneiro Bruno Valiate Cristiane Toledo Andres M. Salazar Otávia Caballero Joseli Lannes-Vieira Santuza R. Teixeira Alexandre B. Reis Ricardo T. Gazzinelli |
| author_facet | Julia T. Castro Rory Brito Natalia S. Hojo-Souza Bárbara Azevedo Natalia Salazar Camila P. Ferreira Caroline Junqueira Ana Paula Fernandes Ronnie Vasconcellos Jamille M. Cardoso Rodrigo D. O. Aguiar-Soares Paula M. A. Vieira Cláudia M. Carneiro Bruno Valiate Cristiane Toledo Andres M. Salazar Otávia Caballero Joseli Lannes-Vieira Santuza R. Teixeira Alexandre B. Reis Ricardo T. Gazzinelli |
| author_sort | Julia T. Castro |
| collection | DOAJ |
| description | Abstract Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production. |
| first_indexed | 2024-03-09T08:16:08Z |
| format | Article |
| id | doaj.art-e2f51b8fe5c94be48992e559b978408e |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T08:16:08Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-e2f51b8fe5c94be48992e559b978408e2023-12-02T22:20:56ZengNature Portfolionpj Vaccines2059-01052023-05-018111410.1038/s41541-023-00676-0ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ diseaseJulia T. Castro0Rory Brito1Natalia S. Hojo-Souza2Bárbara Azevedo3Natalia Salazar4Camila P. Ferreira5Caroline Junqueira6Ana Paula Fernandes7Ronnie Vasconcellos8Jamille M. Cardoso9Rodrigo D. O. Aguiar-Soares10Paula M. A. Vieira11Cláudia M. Carneiro12Bruno Valiate13Cristiane Toledo14Andres M. Salazar15Otávia Caballero16Joseli Lannes-Vieira17Santuza R. Teixeira18Alexandre B. Reis19Ricardo T. Gazzinelli20Centro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo HorizonteUniversidade Federal de Ouro PretoCentro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo HorizonteCentro de Pesquisas Rene Rachou, Fundação Osvaldo CruzCentro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo HorizonteUniversidade Federal de São PauloCentro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo HorizonteCentro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo HorizonteUniversidade Federal de São PauloUniversidade Federal de Ouro PretoUniversidade Federal de Ouro PretoUniversidade Federal de Ouro PretoUniversidade Federal de Ouro PretoCentro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo HorizonteCentro de Pesquisas Rene Rachou, Fundação Osvaldo CruzOncovir, IncOrygen, LTDAFundação Osvaldo CruzCentro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo HorizonteUniversidade Federal de Ouro PretoCentro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo HorizonteAbstract Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production.https://doi.org/10.1038/s41541-023-00676-0 |
| spellingShingle | Julia T. Castro Rory Brito Natalia S. Hojo-Souza Bárbara Azevedo Natalia Salazar Camila P. Ferreira Caroline Junqueira Ana Paula Fernandes Ronnie Vasconcellos Jamille M. Cardoso Rodrigo D. O. Aguiar-Soares Paula M. A. Vieira Cláudia M. Carneiro Bruno Valiate Cristiane Toledo Andres M. Salazar Otávia Caballero Joseli Lannes-Vieira Santuza R. Teixeira Alexandre B. Reis Ricardo T. Gazzinelli ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease npj Vaccines |
| title | ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease |
| title_full | ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease |
| title_fullStr | ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease |
| title_full_unstemmed | ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease |
| title_short | ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas’ disease |
| title_sort | asp 2 trans sialidase chimeric protein induces robust protective immunity in experimental models of chagas disease |
| url | https://doi.org/10.1038/s41541-023-00676-0 |
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