78130 20200729203742.0 doi 10.1016/j.omtm.2019.01.014 sideral 110876 ART-2019-110876 eng (orcid)0000-0003-4155-749X Broset, E. Universidad de Zaragoza MTBVAC-Based TB-HIV Vaccine Is Safe, Elicits HIV-T Cell Responses, and Protects against Mycobacterium tuberculosis in Mice 2019 Access copy available to the general public Unrestricted The tuberculosis (TB) vaccine MTBVAC is the only live-attenuated Mycobacterium tuberculosis (Mtb)-based vaccine in clinical development, and it confers superior protection in different animal models compared to the current vaccine, BCG (Mycobacterium bovis bacillus Calmette-Guérin). With the aim of using MTBVAC as a vector for a dual TB-HIV vaccine, we constructed the recombinant MTBVAC.HIVA 2auxo strain. First, we generated a lysine auxotroph of MTBVAC (MTBVAC¿lys) by deleting the lysA gene. Then the auxotrophic MTBVAC¿lys was transformed with the E. coli-mycobacterial vector p2auxo.HIVA, harboring the lysA-complementing gene and the HIV-1 clade A immunogen HIVA. This TB-HIV vaccine conferred similar efficacy to the parental strain MTBVAC against Mtb challenge in mice. MTBVAC.HIVA 2auxo was safer than BCG and MTBVAC in severe combined immunodeficiency (SCID) mice, and it was shown to be maintained up to 42 bacterial generations in vitro and up to 100 days after inoculation in vivo. The MTBVAC.HIVA 2auxo vaccine, boosted with modified vaccinia virus Ankara (MVA).HIVA, induced HIV-1 and Mtb-specific interferon-¿-producing T cell responses and polyfunctional HIV-1-specific CD8+ T cells producing interferon-¿ (IFN-¿), tumor necrosis factor alpha (TNF-a), and CD107a in BALB/c mice. Here we describe new tools to develop combined vaccines against TB and HIV with the potential of expansion for other infectious diseases. info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P info:eu-repo/grantAgreement/ES/MINECO/BES-2012-052937 info:eu-repo/grantAgreement/ES/ISCIII/RETIC-RIS RD12-0017-0001 info:eu-repo/grantAgreement/ES/ISCIII/RETIC-RIS RD12-0017 info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI14-00494 This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 681137-EAVI2020 info:eu-repo/grantAgreement/EC/H2020/681137/EU/European AIDS Vaccine Initiative 2020/EAVI2020 This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 643381-TBVAC2020 info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020 info:eu-repo/grantAgreement/ES/DGA/FSE info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.533 2019 1.872 2019 MEDICINE, RESEARCH & EXPERIMENTAL 34 / 138 = 0.246 2019 Q1 T1 Genetics 2019 Q1 Molecular Medicine 2019 Q1 Molecular Biology 2019 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Saubi, N. Guitart, N. Aguilo, N. (orcid)0000-0001-7866-2803 Uranga, S. Universidad de Zaragoza Kilpeläinen, A. Eto, Y. Hanke, T. (orcid)0000-0001-8841-6593 Gonzalo-Asensio, J. Universidad de Zaragoza (orcid)0000-0003-2993-5478 Martín, C. Universidad de Zaragoza Joseph-Munné, J. 1008 630 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Microbiología 1008 X Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Proy. investigación HQA 13 (2019), 253-264 Mol. ther., Methods clin. dev. Molecular Therapy-Methods & Clinical Development 2329-0501 713221 http://zaguan.unizar.es/record/78130/files/texto_completo.pdf Versión publicada 128335 http://zaguan.unizar.es/record/78130/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:78130 articulos driver 2020-07-29-20:20:21 ARTICLE