TY - JOUR
T1 - Recombinant BCG-Rv1767 amount determines, in vivo, antigen-specific T cells location, frequency, and protective outcome
AU - Speranza, Viviana
AU - Colone, Alessia
AU - Cicconi, Rosella
AU - Palmieri, Graziana
AU - Giovannini, Daniela
AU - Grassi, Manuela
AU - Mattei, Maurizio
AU - Sali, Michela
AU - Delogu, Giovanni
AU - Andreola, Federica
AU - Colizzi, Vittorio
AU - Mariani, Francesca
PY - 2010/5
Y1 - 2010/5
N2 - 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-α, 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.
AB - 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-α, 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.
KW - Cell mediated immune response
KW - M. tuberculosis gene expression
KW - Organ-specific T helper phenotype
KW - Protection
KW - Recombinant-BCG
KW - TB vaccine
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U2 - 10.1016/j.micpath.2010.02.003
DO - 10.1016/j.micpath.2010.02.003
M3 - Article
C2 - 20219669
AN - SCOPUS:77952956800
VL - 48
SP - 150
EP - 159
JO - Microbial Pathogenesis
JF - Microbial Pathogenesis
SN - 0882-4010
IS - 5
ER -