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.