000078130 001__ 78130
000078130 005__ 20200729203742.0
000078130 0247_ $$2doi$$a10.1016/j.omtm.2019.01.014
000078130 0248_ $$2sideral$$a110876
000078130 037__ $$aART-2019-110876
000078130 041__ $$aeng
000078130 100__ $$0(orcid)0000-0003-4155-749X$$aBroset, E.$$uUniversidad de Zaragoza
000078130 245__ $$aMTBVAC-Based TB-HIV Vaccine Is Safe, Elicits HIV-T Cell Responses, and Protects against Mycobacterium tuberculosis in Mice
000078130 260__ $$c2019
000078130 5060_ $$aAccess copy available to the general public$$fUnrestricted
000078130 5203_ $$aThe 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.
000078130 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P$$9info:eu-repo/grantAgreement/ES/MINECO/BES-2012-052937$$9info:eu-repo/grantAgreement/ES/ISCIII/RETIC-RIS RD12-0017-0001$$9info:eu-repo/grantAgreement/ES/ISCIII/RETIC-RIS RD12-0017$$9info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI14-00494$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 681137-EAVI2020$$9info:eu-repo/grantAgreement/EC/H2020/681137/EU/European AIDS Vaccine Initiative 2020/EAVI2020$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 643381-TBVAC2020$$9info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020$$9info:eu-repo/grantAgreement/ES/DGA/FSE
000078130 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000078130 590__ $$a4.533$$b2019
000078130 592__ $$a1.872$$b2019
000078130 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b34 / 138 = 0.246$$c2019$$dQ1$$eT1
000078130 593__ $$aGenetics$$c2019$$dQ1
000078130 593__ $$aMolecular Medicine$$c2019$$dQ1
000078130 593__ $$aMolecular Biology$$c2019$$dQ1
000078130 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000078130 700__ $$aSaubi, N.
000078130 700__ $$aGuitart, N.
000078130 700__ $$aAguilo, N.
000078130 700__ $$0(orcid)0000-0001-7866-2803$$aUranga, S.$$uUniversidad de Zaragoza
000078130 700__ $$aKilpeläinen, A.
000078130 700__ $$aEto, Y.
000078130 700__ $$aHanke, T.
000078130 700__ $$0(orcid)0000-0001-8841-6593$$aGonzalo-Asensio, J.$$uUniversidad de Zaragoza
000078130 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, C.$$uUniversidad de Zaragoza
000078130 700__ $$aJoseph-Munné, J.
000078130 7102_ $$11008$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Microbiología
000078130 7102_ $$11008$$2X$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cProy. investigación HQA
000078130 773__ $$g13 (2019), 253-264$$pMol. ther., Methods clin. dev.$$tMolecular Therapy-Methods & Clinical Development$$x2329-0501
000078130 8564_ $$s713221$$uhttps://zaguan.unizar.es/record/78130/files/texto_completo.pdf$$yVersión publicada
000078130 8564_ $$s128335$$uhttps://zaguan.unizar.es/record/78130/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000078130 909CO $$ooai:zaguan.unizar.es:78130$$particulos$$pdriver
000078130 951__ $$a2020-07-29-20:20:21
000078130 980__ $$aARTICLE