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...

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Autores principales:	Holgado, M.P., Falivene, J., Maeto, C., Amigo, M., Pascutti, M.F., Vecchione, M.B., Bruttomesso, A., Calamante, G., Del Médico-Zajac, M.P., Gherardi, M.M.
Formato:	JOUR
Materias:	MVA T-cell response Vaccine beta interferon gamma interferon interleukin 12 interleukin 18 binding protein interleukin 1beta virus vaccine A46R protein, vaccinia virus C12L protein, vaccinia virus cytokine epitope viral protein virus antigen A44L gene A46R gene animal cell Article C12L gene cell proliferation controlled study cytokine production cytotoxicity enzyme linked immunospot assay female gene deletion gene expression gene sequence immune response immunofluorescence immunogenicity mouse nonhuman reverse transcription polymerase chain reaction RNA extraction spleen cell T lymphocyte Vaccinia virus virus gene animal C57BL mouse genetics immunology innate immunity lymph node secretion (process) spleen Animals Antigens, Viral Cytokines Epitopes Immunity, Innate Lymph Nodes Mice, Inbred C57BL Sequence Deletion Spleen T-Lymphocytes Viral Proteins
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_19994915_v8_n5_p_Holgado
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_19994915_v8_n5_p_Holgado
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spelling	todo:paper_19994915_v8_n5_p_Holgado2023-10-03T16:37:36Z 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, M.P. Falivene, J. Maeto, C. Amigo, M. Pascutti, M.F. Vecchione, M.B. Bruttomesso, A. Calamante, G. Del Médico-Zajac, M.P. Gherardi, M.M. MVA T-cell response Vaccine beta interferon gamma interferon interleukin 12 interleukin 18 binding protein interleukin 1beta virus vaccine A46R protein, vaccinia virus C12L protein, vaccinia virus cytokine epitope viral protein virus antigen A44L gene A46R gene animal cell Article C12L gene cell proliferation controlled study cytokine production cytotoxicity enzyme linked immunospot assay female gene deletion gene expression gene sequence immune response immunofluorescence immunogenicity mouse nonhuman reverse transcription polymerase chain reaction RNA extraction spleen cell T lymphocyte Vaccinia virus virus gene animal C57BL mouse genetics immunology innate immunity lymph node secretion (process) spleen T lymphocyte Animals Antigens, Viral Cytokines Epitopes Immunity, Innate Lymph Nodes Mice, Inbred C57BL Sequence Deletion Spleen T-Lymphocytes Vaccinia virus Viral Proteins 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. © 2016 by the authors; licensee MDPI, Basel, Switzerland. Fil:Holgado, M.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Falivene, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Maeto, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bruttomesso, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Calamante, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Del Médico-Zajac, M.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gherardi, M.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19994915_v8_n5_p_Holgado
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	MVA T-cell response Vaccine beta interferon gamma interferon interleukin 12 interleukin 18 binding protein interleukin 1beta virus vaccine A46R protein, vaccinia virus C12L protein, vaccinia virus cytokine epitope viral protein virus antigen A44L gene A46R gene animal cell Article C12L gene cell proliferation controlled study cytokine production cytotoxicity enzyme linked immunospot assay female gene deletion gene expression gene sequence immune response immunofluorescence immunogenicity mouse nonhuman reverse transcription polymerase chain reaction RNA extraction spleen cell T lymphocyte Vaccinia virus virus gene animal C57BL mouse genetics immunology innate immunity lymph node secretion (process) spleen T lymphocyte Animals Antigens, Viral Cytokines Epitopes Immunity, Innate Lymph Nodes Mice, Inbred C57BL Sequence Deletion Spleen T-Lymphocytes Vaccinia virus Viral Proteins
spellingShingle	MVA T-cell response Vaccine beta interferon gamma interferon interleukin 12 interleukin 18 binding protein interleukin 1beta virus vaccine A46R protein, vaccinia virus C12L protein, vaccinia virus cytokine epitope viral protein virus antigen A44L gene A46R gene animal cell Article C12L gene cell proliferation controlled study cytokine production cytotoxicity enzyme linked immunospot assay female gene deletion gene expression gene sequence immune response immunofluorescence immunogenicity mouse nonhuman reverse transcription polymerase chain reaction RNA extraction spleen cell T lymphocyte Vaccinia virus virus gene animal C57BL mouse genetics immunology innate immunity lymph node secretion (process) spleen T lymphocyte Animals Antigens, Viral Cytokines Epitopes Immunity, Innate Lymph Nodes Mice, Inbred C57BL Sequence Deletion Spleen T-Lymphocytes Vaccinia virus Viral Proteins Holgado, M.P. Falivene, J. Maeto, C. Amigo, M. Pascutti, M.F. Vecchione, M.B. Bruttomesso, A. Calamante, G. Del Médico-Zajac, M.P. Gherardi, M.M. 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_facet	MVA T-cell response Vaccine beta interferon gamma interferon interleukin 12 interleukin 18 binding protein interleukin 1beta virus vaccine A46R protein, vaccinia virus C12L protein, vaccinia virus cytokine epitope viral protein virus antigen A44L gene A46R gene animal cell Article C12L gene cell proliferation controlled study cytokine production cytotoxicity enzyme linked immunospot assay female gene deletion gene expression gene sequence immune response immunofluorescence immunogenicity mouse nonhuman reverse transcription polymerase chain reaction RNA extraction spleen cell T lymphocyte Vaccinia virus virus gene animal C57BL mouse genetics immunology innate immunity lymph node secretion (process) spleen T lymphocyte Animals Antigens, Viral Cytokines Epitopes Immunity, Innate Lymph Nodes Mice, Inbred C57BL Sequence Deletion Spleen T-Lymphocytes Vaccinia virus Viral Proteins
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. © 2016 by the authors; licensee MDPI, Basel, Switzerland.
format	JOUR
author	Holgado, M.P. Falivene, J. Maeto, C. Amigo, M. Pascutti, M.F. Vecchione, M.B. Bruttomesso, A. Calamante, G. Del Médico-Zajac, M.P. Gherardi, M.M.
author_facet	Holgado, M.P. Falivene, J. Maeto, C. Amigo, M. Pascutti, M.F. Vecchione, M.B. Bruttomesso, A. Calamante, G. Del Médico-Zajac, M.P. Gherardi, M.M.
author_sort	Holgado, M.P.
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_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_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_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
url	http://hdl.handle.net/20.500.12110/paper_19994915_v8_n5_p_Holgado
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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

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