MTBVAC-Based TB-HIV Vaccine Is Safe, Elicits HIV-T Cell Responses, and Protects against Mycobacterium tuberculosis in Mice

Broset, E. (Universidad de Zaragoza) ; Saubi, N. ; Guitart, N. ; Aguilo, N. ; Uranga, S. (Universidad de Zaragoza) ; Kilpeläinen, A. ; Eto, Y. ; Hanke, T. ; Gonzalo-Asensio, J. (Universidad de Zaragoza) ; Martín, C. (Universidad de Zaragoza) ; Joseph-Munné, J.

Resumen: 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.

Idioma: Inglés

DOI: 10.1016/j.omtm.2019.01.014

Año: 2019

Publicado en: Molecular Therapy-Methods & Clinical Development 13 (2019), 253-264
ISSN: 2329-0501

Factor impacto JCR: 4.533 (2019)

Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 34 / 138 = 0.246 (2019) - Q1 - T1

Factor impacto SCIMAGO: 1.872 - Genetics (Q1) - Molecular Medicine (Q1) - Molecular Biology (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/FSE
Financiación: 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
Financiación: info:eu-repo/grantAgreement/EC/H2020/681137/EU/European AIDS Vaccine Initiative 2020/EAVI2020
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI14-00494
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RETIC-RIS RD12-0017
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RETIC-RIS RD12-0017-0001
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BES-2012-052937
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Microbiología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Proy. investigación HQA (Dpto. Microb.Med.Pr.,Sal.Públ.)