title: Recombinant BCG-Rv1767 amount determines, in vivo, antigen-specific T cells location, frequency, and protective outcome.
abstract: One possibility to improve the efficacy of BCG vaccine against TB is to create a recombinant BCG (r-BCG), increasing the expression of mycobacterial antigens, to ameliorate the response to BCG. Here we describe a new r-BCG expressing the gene Rv1767, induced by Mycobacterium tuberculosis during its survival in human macrophages. The r-BCG elicited a specific T cells response in Balb/c mice higher than wt BCG. The r-BCG amount used to immunise mice determined diverse Th1/Th2 equilibriums, which was not the same in spleen and Lymph Nodes. Differences in cytokines production were found for IL-10, IL-4, TNF-alpha, and Arginase-1, which, in some conditions, resulted higher in r-BCG as compared to wt BCG-immunised mice. The immunisation with r-BCG-Rv1767 induced a lesser protective activity than wt BCG in a mouse model of TB. This reduction might likely be explained by the specific T cells phenotype and setting existing before MTB challenge, induced by either the single or the triple dose of r-BCG. The use of this model may help to highlight the capacity of different M. tuberculosis antigens to induce a protective immune response, actually not necessarily embodied by an increased frequency of Antigen-specific effector memory T cells.
authors.affiliation: Institute of Neurobiology and Molecular Medicine, National Research Council, Via del Fosso del Cavaliere 100, 00133 Rome, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Speranza
authors.forename: Alessia
authors.initials: A
authors.lastname: Colone
authors.forename: Rosella
authors.initials: R
authors.lastname: Cicconi
authors.forename: Graziana
authors.initials: G
authors.lastname: Palmieri
authors.forename: Daniela
authors.initials: D
authors.lastname: Giovannini
authors.forename: Manuela
authors.initials: M
authors.lastname: Grassi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mattei
authors.forename: Michela
authors.initials: M
authors.lastname: Sali
authors.forename: Giovanni
authors.initials: G
authors.lastname: Delogu
authors.forename: Federica
authors.initials: F
authors.lastname: Andreola
authors.forename: Vittorio
authors.initials: V
authors.lastname: Colizzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Mariani
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001500:BCG Vaccine / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase