MVAΔ008 viral vector encoding the model protein OVA induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional MVA

Modified vaccinia Ankara virus (MVA) is extensively used as a vaccine vector. We have previously observed that MVAΔ008, an MVA lacking the gene that codes for interleukin-18 binding protein, significantly increases CD8+ and CD4+ T-cell responses to vaccinia virus (VACV) epitopes and recombinant HIV...

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Main Authors: Del Medico Zajac, Maria Paula, Molinari, Maria Paula, Gravisaco, María José, Maizon, Daniel Omar, Moron, Victor Gabriel, Gherardi, Maria Magdalena, Calamante, Gabriela
Format: Artículo
Language:Inglés
Published: Elsevier 2021
Subjects:
Online Access:http://hdl.handle.net/20.500.12123/10777
https://www.sciencedirect.com/science/article/abs/pii/S016158902100242X
https://doi.org/10.1016/j.molimm.2021.08.004
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author Del Medico Zajac, Maria Paula
Molinari, Maria Paula
Gravisaco, María José
Maizon, Daniel Omar
Moron, Victor Gabriel
Gherardi, Maria Magdalena
Calamante, Gabriela
author_browse Calamante, Gabriela
Del Medico Zajac, Maria Paula
Gherardi, Maria Magdalena
Gravisaco, María José
Maizon, Daniel Omar
Molinari, Maria Paula
Moron, Victor Gabriel
author_facet Del Medico Zajac, Maria Paula
Molinari, Maria Paula
Gravisaco, María José
Maizon, Daniel Omar
Moron, Victor Gabriel
Gherardi, Maria Magdalena
Calamante, Gabriela
author_sort Del Medico Zajac, Maria Paula
collection INTA Digital
description Modified vaccinia Ankara virus (MVA) is extensively used as a vaccine vector. We have previously observed that MVAΔ008, an MVA lacking the gene that codes for interleukin-18 binding protein, significantly increases CD8+ and CD4+ T-cell responses to vaccinia virus (VACV) epitopes and recombinant HIV antigens. However, the efficacy of this vector against pathogens or tumor cells remains unclear. Thus, the aim of this study was to evaluate the cellular immune response and the protection induced by recombinant MVAs encoding the model antigen ovalbumin (OVA). We used the MO5 melanoma tumor model (OVA-expressing tumor) as an approach for evaluating the vector-induced efficacy. Our results show that MVAΔ008-OVA (optimized vector) induced higher in vivo specific cytotoxicity and ex vivo T-cell IFN-γ responses against OVA than the conventional MVA vector. Importantly, the recombinant vectors were capable of controlling MO5 tumor growth. Indeed, the administration of MVAΔ008-OVA or MVA-OVA in prophylactic and therapeutic schemes provided total protection and longer survival of mice, respectively. Overall, our results demonstrate the improved immunogenicity and the protective capacity of MVAΔ008 against a heterologous model antigen. These findings suggest that MVAΔ008 constitutes an excellent candidate for vaccine development against pathogens or cancer therapy.
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spelling INTA107772021-11-15T14:28:34Z MVAΔ008 viral vector encoding the model protein OVA induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional MVA Del Medico Zajac, Maria Paula Molinari, Maria Paula Gravisaco, María José Maizon, Daniel Omar Moron, Victor Gabriel Gherardi, Maria Magdalena Calamante, Gabriela Vacuna Vectores Respuesta Inmunológica Genética Vaccines Vectors Immune Response Genetics Modified vaccinia Ankara virus (MVA) is extensively used as a vaccine vector. We have previously observed that MVAΔ008, an MVA lacking the gene that codes for interleukin-18 binding protein, significantly increases CD8+ and CD4+ T-cell responses to vaccinia virus (VACV) epitopes and recombinant HIV antigens. However, the efficacy of this vector against pathogens or tumor cells remains unclear. Thus, the aim of this study was to evaluate the cellular immune response and the protection induced by recombinant MVAs encoding the model antigen ovalbumin (OVA). We used the MO5 melanoma tumor model (OVA-expressing tumor) as an approach for evaluating the vector-induced efficacy. Our results show that MVAΔ008-OVA (optimized vector) induced higher in vivo specific cytotoxicity and ex vivo T-cell IFN-γ responses against OVA than the conventional MVA vector. Importantly, the recombinant vectors were capable of controlling MO5 tumor growth. Indeed, the administration of MVAΔ008-OVA or MVA-OVA in prophylactic and therapeutic schemes provided total protection and longer survival of mice, respectively. Overall, our results demonstrate the improved immunogenicity and the protective capacity of MVAΔ008 against a heterologous model antigen. These findings suggest that MVAΔ008 constitutes an excellent candidate for vaccine development against pathogens or cancer therapy. Instituto de Biotecnología Fil: Del Medico Zajac, Maria Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Del Medico Zajac, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Molinari, Maria Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Molinari, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gravisaco, Marí­a José. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Gravisaco, Marí­a José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Maizon, Daniel Omar Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Anguil; Argentina Fil: Moron, Victor Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Moron, Victor Gabriel. Universidad Nacional de Córdoba.Facultad de Ciencias Químicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; 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; Argentina Fil: Gherardi, Maria Magdalena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Fil: Calamante, Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina Fil: Calamante, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 2021-11-15T14:24:41Z 2021-11-15T14:24:41Z 2021-11 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/10777 https://www.sciencedirect.com/science/article/abs/pii/S016158902100242X 0161-5890 https://doi.org/10.1016/j.molimm.2021.08.004 eng info:eu-repograntAgreement/INTA/PNBIO-1131032/AR./Desarrollo de herramientas biotecnológicas para la prevención y el control de enfermedades pecuarias: vacunas, diagnóstico y eIdemiología molecular. info:eu-repo/semantics/restrictedAccess application/pdf Elsevier Molecular Immunology 139 : 115-122 (November 2021)
spellingShingle Vacuna
Vectores
Respuesta Inmunológica
Genética
Vaccines
Vectors
Immune Response
Genetics
Del Medico Zajac, Maria Paula
Molinari, Maria Paula
Gravisaco, María José
Maizon, Daniel Omar
Moron, Victor Gabriel
Gherardi, Maria Magdalena
Calamante, Gabriela
MVAΔ008 viral vector encoding the model protein OVA induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional MVA
title MVAΔ008 viral vector encoding the model protein OVA induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional MVA
title_full MVAΔ008 viral vector encoding the model protein OVA induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional MVA
title_fullStr MVAΔ008 viral vector encoding the model protein OVA induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional MVA
title_full_unstemmed MVAΔ008 viral vector encoding the model protein OVA induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional MVA
title_short MVAΔ008 viral vector encoding the model protein OVA induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional MVA
title_sort mvaδ008 viral vector encoding the model protein ova induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional mva
topic Vacuna
Vectores
Respuesta Inmunológica
Genética
Vaccines
Vectors
Immune Response
Genetics
url http://hdl.handle.net/20.500.12123/10777
https://www.sciencedirect.com/science/article/abs/pii/S016158902100242X
https://doi.org/10.1016/j.molimm.2021.08.004
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