IL-12 DNA Displays efficient adjuvant effects improving immunogenicity of Ag85A in DNA prime/MVA boost immunizations
Mycobacterium tuberculosis (Mtb) infection is one of the leading causes of death worldwide. The Modified Vaccinia Ankara (MVA) vaccine vector expressing the mycobacterial antigen 85A (MVA85A) was demonstrated to be safe, although it did not improve BCG efficacy, denoting the need to search for impro...
| Autores principales: | , , , , , , , |
|---|---|
| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
Frontiers Media
2021
|
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12123/8630 https://www.frontiersin.org/articles/10.3389/fcimb.2020.581812/full https://doi.org/10.3389/fcimb.2020.581812 |
| _version_ | 1855484237490159616 |
|---|---|
| author | Morelli, María Paula Del Medico Zajac, Maria Paula Pellegrini, Joaquín Miguel Amiano, Nicolás Oscar Tateosian, Nancy Liliana Calamante, Gabriela Gherardi, Maria Magdalena García, Verónica Edith |
| author_browse | Amiano, Nicolás Oscar Calamante, Gabriela Del Medico Zajac, Maria Paula García, Verónica Edith Gherardi, Maria Magdalena Morelli, María Paula Pellegrini, Joaquín Miguel Tateosian, Nancy Liliana |
| author_facet | Morelli, María Paula Del Medico Zajac, Maria Paula Pellegrini, Joaquín Miguel Amiano, Nicolás Oscar Tateosian, Nancy Liliana Calamante, Gabriela Gherardi, Maria Magdalena García, Verónica Edith |
| author_sort | Morelli, María Paula |
| collection | INTA Digital |
| description | Mycobacterium tuberculosis (Mtb) infection is one of the leading causes of death worldwide. The Modified Vaccinia Ankara (MVA) vaccine vector expressing the mycobacterial antigen 85A (MVA85A) was demonstrated to be safe, although it did not improve BCG efficacy, denoting the need to search for improved tuberculosis vaccines. In this work, we investigated the effect of IL-12 DNA -as an adjuvant- on an Ag85A DNA prime/MVA85A boost vaccination regimen. We evaluated the immune response profile elicited in mice and the protection conferred against intratracheal Mtb H37Rv challenge. We observed that the immunization scheme including DNA-A85A+DNA-IL-12/MVA85A induced a strong IFN-γ production to Ag85A in vitro, with a significant expansion of IFN-γ+CD4+ and IFN-γ+CD8+ anti-Ag85A lymphocytes. Furthermore, we also detected a significant increase in the proportion of specific CD8+CD107+ T cells against Ag85A. Additionally, inclusion of IL-12 DNA in the DNA-A85A/MVA85A vaccine scheme induced a marked augment in anti-Ag85A IgG levels. Interestingly, after 30 days of infection with Mtb H37Rv, DNA-A85A+DNA-IL-12/MVA85A vaccinated mice displayed a significant reduction in lung bacterial burden. Together, our findings suggest that IL-12 DNA might be useful as a molecular adjuvant in an Ag85A DNA/MVA prime-boost vaccine against Mtb infection. |
| format | Artículo |
| id | INTA8630 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Frontiers Media |
| publisherStr | Frontiers Media |
| record_format | dspace |
| spelling | INTA86302021-01-21T13:22:33Z IL-12 DNA Displays efficient adjuvant effects improving immunogenicity of Ag85A in DNA prime/MVA boost immunizations Morelli, María Paula Del Medico Zajac, Maria Paula Pellegrini, Joaquín Miguel Amiano, Nicolás Oscar Tateosian, Nancy Liliana Calamante, Gabriela Gherardi, Maria Magdalena García, Verónica Edith Vaccine Adjuvants Immunogenetics Coadyuvantes de Vacunas Tuberculosis Mycobacterium Tuberculosis Inmunogenética Ag85A IL-12, MVA Mycobacterium tuberculosis (Mtb) infection is one of the leading causes of death worldwide. The Modified Vaccinia Ankara (MVA) vaccine vector expressing the mycobacterial antigen 85A (MVA85A) was demonstrated to be safe, although it did not improve BCG efficacy, denoting the need to search for improved tuberculosis vaccines. In this work, we investigated the effect of IL-12 DNA -as an adjuvant- on an Ag85A DNA prime/MVA85A boost vaccination regimen. We evaluated the immune response profile elicited in mice and the protection conferred against intratracheal Mtb H37Rv challenge. We observed that the immunization scheme including DNA-A85A+DNA-IL-12/MVA85A induced a strong IFN-γ production to Ag85A in vitro, with a significant expansion of IFN-γ+CD4+ and IFN-γ+CD8+ anti-Ag85A lymphocytes. Furthermore, we also detected a significant increase in the proportion of specific CD8+CD107+ T cells against Ag85A. Additionally, inclusion of IL-12 DNA in the DNA-A85A/MVA85A vaccine scheme induced a marked augment in anti-Ag85A IgG levels. Interestingly, after 30 days of infection with Mtb H37Rv, DNA-A85A+DNA-IL-12/MVA85A vaccinated mice displayed a significant reduction in lung bacterial burden. Together, our findings suggest that IL-12 DNA might be useful as a molecular adjuvant in an Ag85A DNA/MVA prime-boost vaccine against Mtb infection. Instituto de Biotecnología Fil: Morelli, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fil: Del Medico Zajac, Maria Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Fil: Pellegrini, Joaquín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fil: Tateosian, Nancy Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fil: Calamante, Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina. Fil: Gherardi, Maria Magdalena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Fil: García, Verónica Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fil: Pellegrini, Joaquín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fil: Pellegrini, Joaquín Miguel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica; Argentina. Fil: Pellegrini, Joaquín Miguel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Morelli, María Paula. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica; Argentina. Fil: Morelli, María Paula. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Del Medico Zajac, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Amiano, Nicolás Oscar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica; Argentina. Fil: Amiano, Nicolás Oscar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Tateosian, Nancy Liliana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica; Argentina. Fil: Tateosian, Nancy Liliana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Calamante, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gherardi, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: García, Verónica Edith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica; Argentina. Fil: García, Verónica Edith. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina 2021-01-21T13:03:57Z 2021-01-21T13:03:57Z 2020-09 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/8630 https://www.frontiersin.org/articles/10.3389/fcimb.2020.581812/full 2235-2988 https://doi.org/10.3389/fcimb.2020.581812 eng info:eu-repograntAgreement/INTA/2019-PD-E5-I102-001/2019-PD-E5-I102-001/AR./Desarrollo de vacunas y tecnologías para mejorar las estrategias profilácticas y terapéuticas de las enfermedades que afectan la producción animal y la salud pública 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 Frontiers Media Frontiers in cellular and infection microbiology 10 : 581812. (Septiembre 2020) |
| spellingShingle | Vaccine Adjuvants Immunogenetics Coadyuvantes de Vacunas Tuberculosis Mycobacterium Tuberculosis Inmunogenética Ag85A IL-12, MVA Morelli, María Paula Del Medico Zajac, Maria Paula Pellegrini, Joaquín Miguel Amiano, Nicolás Oscar Tateosian, Nancy Liliana Calamante, Gabriela Gherardi, Maria Magdalena García, Verónica Edith IL-12 DNA Displays efficient adjuvant effects improving immunogenicity of Ag85A in DNA prime/MVA boost immunizations |
| title | IL-12 DNA Displays efficient adjuvant effects improving immunogenicity of Ag85A in DNA prime/MVA boost immunizations |
| title_full | IL-12 DNA Displays efficient adjuvant effects improving immunogenicity of Ag85A in DNA prime/MVA boost immunizations |
| title_fullStr | IL-12 DNA Displays efficient adjuvant effects improving immunogenicity of Ag85A in DNA prime/MVA boost immunizations |
| title_full_unstemmed | IL-12 DNA Displays efficient adjuvant effects improving immunogenicity of Ag85A in DNA prime/MVA boost immunizations |
| title_short | IL-12 DNA Displays efficient adjuvant effects improving immunogenicity of Ag85A in DNA prime/MVA boost immunizations |
| title_sort | il 12 dna displays efficient adjuvant effects improving immunogenicity of ag85a in dna prime mva boost immunizations |
| topic | Vaccine Adjuvants Immunogenetics Coadyuvantes de Vacunas Tuberculosis Mycobacterium Tuberculosis Inmunogenética Ag85A IL-12, MVA |
| url | http://hdl.handle.net/20.500.12123/8630 https://www.frontiersin.org/articles/10.3389/fcimb.2020.581812/full https://doi.org/10.3389/fcimb.2020.581812 |
| work_keys_str_mv | AT morellimariapaula il12dnadisplaysefficientadjuvanteffectsimprovingimmunogenicityofag85aindnaprimemvaboostimmunizations AT delmedicozajacmariapaula il12dnadisplaysefficientadjuvanteffectsimprovingimmunogenicityofag85aindnaprimemvaboostimmunizations AT pellegrinijoaquinmiguel il12dnadisplaysefficientadjuvanteffectsimprovingimmunogenicityofag85aindnaprimemvaboostimmunizations AT amianonicolasoscar il12dnadisplaysefficientadjuvanteffectsimprovingimmunogenicityofag85aindnaprimemvaboostimmunizations AT tateosiannancyliliana il12dnadisplaysefficientadjuvanteffectsimprovingimmunogenicityofag85aindnaprimemvaboostimmunizations AT calamantegabriela il12dnadisplaysefficientadjuvanteffectsimprovingimmunogenicityofag85aindnaprimemvaboostimmunizations AT gherardimariamagdalena il12dnadisplaysefficientadjuvanteffectsimprovingimmunogenicityofag85aindnaprimemvaboostimmunizations AT garciaveronicaedith il12dnadisplaysefficientadjuvanteffectsimprovingimmunogenicityofag85aindnaprimemvaboostimmunizations |