One-third of the world's human population is latently infected with Mycobacterium tuberculosis (M. tb), and adult tuberculosis (TB) is largely caused by the resuscitation of latent M. tb. Rv2660c, an M. tb dormancy-related antigen, is preferentially expressed during latent infection. Identification and characterization of Rv2660c are crucial to understanding host-pathogen interactions and to develop drug target and vaccine candidates. In this study, T-cell and antibody immune responses against recombinant Rv2660c protein were respectively investigated in latent M. tb infection (LTBI) cases, pulmonary tuberculosis (PTB) patients, and healthy individuals (HI). After stimulation with recombinant Rv2660c protein, stronger cellular responses were induced in LTBI cases compared with those in PTB patients or in HI. Meanwhile, Rv2660c stimulated higher levels of IgG, IgG1, and IgG2a antibody titers in LTBI cases compared with those in PTB patients. The results showed that Rv2660c is able to elicit prominent cellular immune responses and strong humoral immunity in a Chinese LTBI population, suggesting that Rv2660c is a potential target to develop new vaccines and drugs to control LTBI.
ESAT-6 protein of Mycobacterium tuberculosis is absent in Mycobacterium bovis BCG and Mycobacterium microti and has been demonstrated to stimulate strong cell-mediated immunity. IL-12 can play crucial roles in regulating IFN-γ production and Th1 effectors production. In this study, we constructed three rBCG vaccines that could express proteins of human IL-12p70 and/or ESAT-6 and evaluated their immunogenicity and protective efficacy in mice. Our experiments illustrated that the rBCG-IE (expressing a fusion protein of human IL-12p70 and ESAT-6) was capable of inducing stronger Th1 type cell-mediated immune responses than conventional BCG, or rBCG-I (expressing human IL-12p70), or rBCG-E (expressing ESAT-6). However, the results of protective experiments showed that rBCG-IE could only confer similar and even lower protective efficacy against M. tuberculosis H37Rv infection compared with BCG vaccine.
Early secretory antigen target 6 (ESAT‐6) is a dominant target for cell‐mediated immunity in the early phase of tuberculosis (TB) in patients with TB, causing T‐cell proliferation and gamma interferon (IFN‐γ) production, which has been considered to be a protective antigen that can be used for future vaccine development. Ag85A is the most essential component for bacterial survival within macrophages and has been used in numerous vaccine preparations, which can induce strong cellular immune responses. In this study, we constructed a new recombinant bacilli Calmette‐Guérin (BCG) strain (rBCG‐AE) that could express fusion protein Ag85A‐ESAT‐6 of Mycobacterium tuberculosis and evaluated its immunogenicity in BALB/c mice. There was no evidence for increased virulence of this rBCG. Our experiments illustrated that the rBCG‐AE was able to induce higher titer of antibody and elicit more long‐lasting and stronger Th1 type cellular immune responses than the parental BCG strain, or rBCG‐A (expressing Ag85A) strain, or rBCG‐E (expressing ESAT‐6) strain, which are characterized by the strong antibody response, the proliferation rate of splenocytes, the ratio of CD4+ T and CD8+ T cells stimulated by tuberculin‐purified protein derivative and elevated levels of IFN‐γ in antigen‐stimulated splenocyte cultures. The results show that rBCG‐AE is an improved TB vaccine for further study.
Since Mycobacterium bovis bacillus Calmette2Guerin strain (BCG) fails to protect adults from pulmonary tuberculosis (TB), there is an urgent need for developing a new vaccine. In this study, we constructed a novel recombinant BCG strain (rBCG) expressing human granulocyte macrophage colony-stimulating factor (GM-CSF) and the 6 kDa early secretory antigenic target (ESAT6) of Mycobacterium tuberculosis, named rBCG:GE (expressing GMCSF-ESAT6 complex), and evaluated the immunogenicity of the construct in BALB/c mice. Our results indicated that the rBCG:GE was able to induce higher titer of antibody than the conventional BCG, the rBCG:G (expressing GM-CSF) and the rBCG:E (expressing ESAT6). Moreover, the rBCG:GE also elicited a longer-lasting and stronger Th1 cellular immune responses than the other groups, which was confirmed by the incremental proliferation of splenocytes, the increased percentages of CD4 1 and CD8 1 T cells of spleen, the elevated level of interferon-g in splenocyte culture after tuberculin-purified protein derivative stimulation, and the increased concentration of GM-CSF in serum. The data presented here suggested the possibility that the recombinant BCG:GE might be a good vaccine candidate to TB.
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