Deletion of A44L, A46R and C12L vaccinia virus genes from the MVA genome improved the vector immunogenicity by modifying the innate immune response generating enhanced and optimized specific T-Cell responses
MVA is an attenuated vector that still retains immunomodulatory genes. We have previously reported its optimization after deleting the C12L gene, coding for the IL-18 binding-protein. Here, we analyzed the immunogenicity of MVA vectors harboring the simultaneous deletion of A44L, related to steroid...
| Autores principales: | , , , , , , , , , |
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| Formato: | info:ar-repo/semantics/artículo |
| Lenguaje: | Inglés |
| Publicado: |
2017
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12123/1116 http://www.mdpi.com/1999-4915/8/5/139 https://doi.org/10.3390/v8050139 |
| _version_ | 1855034750804164608 |
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| author | Holgado, María Pía Falivene, Juliana Maeto, Cynthia Amigo, Micaela Pascutti, María Fernanda Vecchione, María Belén Bruttomesso, Andrea Calamante, Gabriela Del Medico Zajac, Maria Paula Gherardi, Maria Magdalena |
| author_browse | Amigo, Micaela Bruttomesso, Andrea Calamante, Gabriela Del Medico Zajac, Maria Paula Falivene, Juliana Gherardi, Maria Magdalena Holgado, María Pía Maeto, Cynthia Pascutti, María Fernanda Vecchione, María Belén |
| author_facet | Holgado, María Pía Falivene, Juliana Maeto, Cynthia Amigo, Micaela Pascutti, María Fernanda Vecchione, María Belén Bruttomesso, Andrea Calamante, Gabriela Del Medico Zajac, Maria Paula Gherardi, Maria Magdalena |
| author_sort | Holgado, María Pía |
| collection | INTA Digital |
| description | MVA is an attenuated vector that still retains immunomodulatory genes. We have previously reported its optimization after deleting the C12L gene, coding for the IL-18 binding-protein. Here, we analyzed the immunogenicity of MVA vectors harboring the simultaneous deletion of A44L, related to steroid synthesis and A46R, a TLR-signaling inhibitor (MVAΔA44L-A46R); or also including a deletion of C12L (MVAΔC12L/ΔA44L-A46R). The absence of biological activities of the deleted genes in the MVA vectors was demonstrated. Adaptive T-cell responses against VACV epitopes, evaluated in spleen and draining lymph-nodes of C57Bl/6 mice at acute/memory phases, were of higher magnitude in those animals that received deleted MVAs compared to MVAwt. MVAΔC12L/ΔA44L-A46R generated cellular specific memory responses of higher quality characterized by bifunctionality (CD107a/b+/IFN-γ+) and proliferation capacity. Deletion of selected genes from MVA generated innate immune responses with higher levels of determining cytokines related to T-cell response generation, such as IL-12, IFN-γ, as well as IL-1β and IFN-β. This study describes for the first time that simultaneous deletion of the A44L, A46R and C12L genes from MVA improved its immunogenicity by enhancing the host adaptive and innate immune responses, suggesting that this approach comprises an appropriate strategy to increase the MVA vaccine potential |
| format | info:ar-repo/semantics/artículo |
| id | INTA1116 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| record_format | dspace |
| spelling | INTA11162019-10-18T16:40:49Z Deletion of A44L, A46R and C12L vaccinia virus genes from the MVA genome improved the vector immunogenicity by modifying the innate immune response generating enhanced and optimized specific T-Cell responses Holgado, María Pía Falivene, Juliana Maeto, Cynthia Amigo, Micaela Pascutti, María Fernanda Vecchione, María Belén Bruttomesso, Andrea Calamante, Gabriela Del Medico Zajac, Maria Paula Gherardi, Maria Magdalena Genética Genetics T-lymphocytes Vaccines Vectors Immunogenetics Linfocitos-t Vectores Inmunogenética MVA is an attenuated vector that still retains immunomodulatory genes. We have previously reported its optimization after deleting the C12L gene, coding for the IL-18 binding-protein. Here, we analyzed the immunogenicity of MVA vectors harboring the simultaneous deletion of A44L, related to steroid synthesis and A46R, a TLR-signaling inhibitor (MVAΔA44L-A46R); or also including a deletion of C12L (MVAΔC12L/ΔA44L-A46R). The absence of biological activities of the deleted genes in the MVA vectors was demonstrated. Adaptive T-cell responses against VACV epitopes, evaluated in spleen and draining lymph-nodes of C57Bl/6 mice at acute/memory phases, were of higher magnitude in those animals that received deleted MVAs compared to MVAwt. MVAΔC12L/ΔA44L-A46R generated cellular specific memory responses of higher quality characterized by bifunctionality (CD107a/b+/IFN-γ+) and proliferation capacity. Deletion of selected genes from MVA generated innate immune responses with higher levels of determining cytokines related to T-cell response generation, such as IL-12, IFN-γ, as well as IL-1β and IFN-β. This study describes for the first time that simultaneous deletion of the A44L, A46R and C12L genes from MVA improved its immunogenicity by enhancing the host adaptive and innate immune responses, suggesting that this approach comprises an appropriate strategy to increase the MVA vaccine potential Fil: Holgado, María Pía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Falivene, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Maeto, Cynthia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Amigo, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Pascutti, María Fernanda. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vecchione, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas En Retrovirus y Sida; Argentina Fil: Bruttomesso, Andrea. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica. Unidad de Microanálisis y Métodos Físicos Aplicados a Química Orgánica; Argentina Fil: Calamante, Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Médico Zajac, María Paula del. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Gherardi, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina 2017-09-04T14:24:55Z 2017-09-04T14:24:55Z 2016-05 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/1116 http://www.mdpi.com/1999-4915/8/5/139 1999-4915 https://doi.org/10.3390/v8050139 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf |
| spellingShingle | Genética Genetics T-lymphocytes Vaccines Vectors Immunogenetics Linfocitos-t Vectores Inmunogenética Holgado, María Pía Falivene, Juliana Maeto, Cynthia Amigo, Micaela Pascutti, María Fernanda Vecchione, María Belén Bruttomesso, Andrea Calamante, Gabriela Del Medico Zajac, Maria Paula Gherardi, Maria Magdalena Deletion of A44L, A46R and C12L vaccinia virus genes from the MVA genome improved the vector immunogenicity by modifying the innate immune response generating enhanced and optimized specific T-Cell responses |
| title | Deletion of A44L, A46R and C12L vaccinia virus genes from the MVA genome improved the vector immunogenicity by modifying the innate immune response generating enhanced and optimized specific T-Cell responses |
| title_full | Deletion of A44L, A46R and C12L vaccinia virus genes from the MVA genome improved the vector immunogenicity by modifying the innate immune response generating enhanced and optimized specific T-Cell responses |
| title_fullStr | Deletion of A44L, A46R and C12L vaccinia virus genes from the MVA genome improved the vector immunogenicity by modifying the innate immune response generating enhanced and optimized specific T-Cell responses |
| title_full_unstemmed | Deletion of A44L, A46R and C12L vaccinia virus genes from the MVA genome improved the vector immunogenicity by modifying the innate immune response generating enhanced and optimized specific T-Cell responses |
| title_short | Deletion of A44L, A46R and C12L vaccinia virus genes from the MVA genome improved the vector immunogenicity by modifying the innate immune response generating enhanced and optimized specific T-Cell responses |
| title_sort | deletion of a44l a46r and c12l vaccinia virus genes from the mva genome improved the vector immunogenicity by modifying the innate immune response generating enhanced and optimized specific t cell responses |
| topic | Genética Genetics T-lymphocytes Vaccines Vectors Immunogenetics Linfocitos-t Vectores Inmunogenética |
| url | http://hdl.handle.net/20.500.12123/1116 http://www.mdpi.com/1999-4915/8/5/139 https://doi.org/10.3390/v8050139 |
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