Modulation of immune responses in mice to recombinant antigens from PE and PPE families of proteins of Mycobacterium tuberculosis by the Ribi adjuvant

Abstract

Three proteins of PE and PPE families of Mycobacterium tuberculosis were evaluated for their ability to induce T cell responses in mice. To enhance immunity induced by protein immunization, we tested the efficacy of adjuvant Ribi (monophosphoryl lipid A+TDM), along with three proteins of the PE/PPE family. Balb/c mice were subcutaneously injected with recombinant proteins, encoded by Rv1818c, Rv3018c and Rv3812 genes of M. tuberculosis H37Rv, formulated with Ribi or IFA for comparative study. Sera from mice immunized with Ribi revealed an increase in the specific immunoglobulin G titers by twofold against Ribi than in mice immunized with IFA. Ribi also elicited stronger delayed-type hypersensitivity and cytotoxic T-lymphocyte activity against the recombinant proteins when compared with IFA. Antigen specific IgG subclass analysis showed that Ribi tends to facilitate IgG2a production, suggesting enhancement of predominant Th1 response which in turn may facilitate increased production of protective IFN-gamma. Furthermore, Ribi preparation increased the number of T cells secreting IFN-gamma. These results indicate that Ribi acts as an effective adjuvant for immune response to antigens of M. tuberculosis. For the first time, we demonstrate that Rv3018c, Rv1818c and Rv3812 proteins of PE/PPE family are T cell antigens with vaccine potential.