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Abstract:

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.

Registro:

Documento: Artículo
Título: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
Autor: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.
Filiación:Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Facultad de Medicina, Ciudad de Buenos Aires, 1121, Argentina
Unidad de Microanálisis y Métodos Físicos Aplicados a Química Orgánica (UMYMFOR), Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, 1428, Argentina
Instituto de Biotecnología, CICVyA-INTA Castelar, Buenos Aires, 1686, Argentina
Sanquin Research, Department of Hematopoiesis, Amsterdam, 1066CX, Netherlands
Palabras clave: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
Año:2016
Volumen:8
Número:5
DOI: http://dx.doi.org/10.3390/v8050139
Título revista:Viruses
Título revista abreviado:Viruses
ISSN:19994915
CAS:gamma interferon, 82115-62-6; interleukin 12, 138415-13-1; interleukin 18 binding protein, 220712-29-8; A46R protein, vaccinia virus; Antigens, Viral; C12L protein, vaccinia virus; Cytokines; Epitopes; Viral Proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19994915_v8_n5_p_Holgado

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Citas:

---------- APA ----------
Holgado, M.P., Falivene, J., Maeto, C., Amigo, M., Pascutti, M.F., Vecchione, M.B., Bruttomesso, A.,..., Gherardi, M.M. (2016) . 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. Viruses, 8(5).
http://dx.doi.org/10.3390/v8050139
---------- CHICAGO ----------
Holgado, M.P., Falivene, J., Maeto, C., Amigo, M., Pascutti, M.F., Vecchione, M.B., et al. "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" . Viruses 8, no. 5 (2016).
http://dx.doi.org/10.3390/v8050139
---------- MLA ----------
Holgado, M.P., Falivene, J., Maeto, C., Amigo, M., Pascutti, M.F., Vecchione, M.B., et al. "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" . Viruses, vol. 8, no. 5, 2016.
http://dx.doi.org/10.3390/v8050139
---------- VANCOUVER ----------
Holgado, M.P., Falivene, J., Maeto, C., Amigo, M., Pascutti, M.F., Vecchione, M.B., et al. 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. Viruses. 2016;8(5).
http://dx.doi.org/10.3390/v8050139