Recombinant BCG-Rv1767 amount determines, in vivo, antigen-specific T cells location, frequency, and protective outcome

Michela Sali, Giovanni Delogu, Giuseppe Palmieri, Viviana Speranza, Alessia Colone, Rosella Cicconi, Graziana Palmieri, Daniela Giovannini, Manuela Grassi, Maurizio Mattei, Federica Andreola, Vittorio Colizzi, Francesca Mariani

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)150-159
Number of pages10
JournalMicrobial Pathogenesis
Volume48
DOIs
Publication statusPublished - 2010

Keywords

  • Animals
  • Antigens, Bacterial
  • Arginase
  • BCG Vaccine
  • Humans
  • Interferon-gamma
  • Interleukin-10
  • Interleukin-4
  • Lymphoid Tissue
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium bovis
  • Mycobacterium tuberculosis
  • Nitric Oxide Synthase Type II
  • T-Lymphocytes
  • T-Lymphocytes, Helper-Inducer
  • Tuberculosis
  • Tumor Necrosis Factor-alpha
  • Vaccines, Synthetic

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