Web of Science: 8 cites, Scopus: 9 cites, Google Scholar: cites
Engineering new mycobacterial vaccine design for HIV–TB pediatric vaccine vectored by lysine auxotroph of BCG
Saubi, Narcís (Universitat de Barcelona. Hospital Clínic. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). AIDS Research Group)
Gea-Mallorquí, Ester (Universitat de Barcelona. Hospital Clínic. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). AIDS Research Group)
Ferrer i Alegre, Pau (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Hurtado, Carmen (Universitat de Barcelona. Hospital Clínic. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). AIDS Research Group)
Sánchez-Úbeda, Sara (Universitat de Barcelona. Hospital Clínic. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). AIDS Research Group)
Eto, Yoshiki (Universitat de Barcelona. Hospital Clínic. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). AIDS Research Group)
Gatell, Josep M (Universitat de Barcelona. Hospital Clínic. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). AIDS Research Group)
Hanke, Tomáš (University of Oxford. Weatherall Institute of Molecular Medicine. MRC Human Immunology Unit)
Joseph, Joan (Universitat de Barcelona. Hospital Clínic. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS). AIDS Research Group)

Data: 2014
Resum: In this study, we have engineered a new mycobacterial vaccine design by using an antibiotic-free plasmid selection system. We assembled a novel Escherichia coli (E. coli)–mycobacterial shuttle plasmid p2auxo. HIVA, expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance based on glycine complementation in E. coli and lysine complementation in mycobacteria. This plasmid was first transformed into glycine auxotroph of E. coli strain and subsequently transformed into lysine auxotroph of Mycobacterium bovis BCG strain to generate vaccine BCG. HIVA 2auxo. We demonstrated that the episomal plasmid p2auxo. HIVA was stable in vivo over a 7-week period and genetically and phenotypically characterized the BCG. HIVA 2auxo vaccine strain. The BCG. HIVA 2auxo vaccine in combination with modified vaccinia virus Ankara (MVA). HIVA was safe and induced HIV-1 and Mycobacterium tuberculosis -specific interferon-γ-producing T-cell responses in adult BALB/c mice. Polyfunctional HIV-1-specific CD8+ T cells, which produce interferon-γ and tumor necrosis factor-α and express the degranulation marker CD107a, were induced. Thus, we engineered a novel, safer, good laboratory practice–compatible BCG-vectored vaccine using prototype immunogen HIVA. This antibiotic-free plasmid selection system based on "double" auxotrophic complementation might be a new mycobacterial vaccine platform to develop not only recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens but also other major pediatric pathogens to prime protective response soon after birth.
Nota: Número d'acord de subvenció ISCIII/PI11-00284
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Llengua: Anglès.
Document: article ; publishedVersion
Publicat a: Molecular Therapy. Methods & Clinical Development, Vol. 1 (May 2014) , art. 14017, ISSN 2329-0501

PMID: 26015961
DOI: 10.1038/mtm.2014.17


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