Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

Responsible for 9 million new cases of active disease and nearly 2 million deaths each year, tuberculosis (TB) remains a global health threat of overwhelming dimensions. Mycobacterium bovis BCG, the only licensed vaccine available, fails to confer lifelong protection and to prevent reactivation of latent infection. Although 15 new vaccine candidates are now in clinical trials, an effective vaccine against TB remains elusive, and new strategies for vaccination are vital. BCG vaccination fails to induce immunity against Mycobacterium tuberculosis latency antigens. Synthetic long peptides (SLPs) combined with adjuvants have been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved to induce efficient antitumor immunity. This study investigated an SLP derived from Rv1733c, a major M. tuberculosis latency antigen which is highly expressed by “dormant” M. tuberculosis and well recognized by T cells from latently M. tuberculosis-infected individuals. In order to assess its in vivo immunogenicity and protective capacity, Rv1733c SLP in CpG was administered to HLA-DR3 transgenic mice. Immunization with Rv1733c SLP elicited gamma interferon-positive/tumor necrosis factor-positive (IFN-γ⁺/TNF⁺) and IFN-γ⁺ CD4⁺ T cells and Rv1733c-specific antibodies and led to a significant reduction in the bacterial load in the lungs of M. tuberculosis-challenged mice. This was observed both in a pre- and in a post-M. tuberculosis challenge setting. Moreover, Rv1733c SLP immunization significantly boosted the protective efficacy of BCG, demonstrating the potential of M. tuberculosis latency antigens to improve BCG efficacy. These data suggest a promising role for M. tuberculosis latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a prophylactic and in a postinfection setting.     

Identification of Rv2041c, a Novel Immunogenic Antigen from Mycobacterium tuberculosis with Serodiagnostic Potential

Factor H plays a key inhibitory role in control of the activation of alternative pathway of complement system. The aim of the study was to investigate the predictive value of factor H as a biomarker of renal injury in IgA nephropathy (IgAN). Urine factor H concentration from 202 patients was measured and compared with that of 60 healthy volunteers. Forty-eight patients fulfilled Haas-I or II (group 1), 60 fulfilled Haas-III (group 2) and 94 fulfilled Haas-IV or V (group 3). Co-deposition of factor H and C3b in kidneys were investigated using confocal microscope. The levels of urinary factor H, when expressed as a ratio of urinary creatinine, were significantly higher in groups 3 than group 1 and 2, also significantly higher in group 2 than group 1. In addition, the levels of urinary factor H were significantly higher in those with factor H deposition in the kidney than those without deposition. The levels of urinary factor H may be a useful biomarker to evaluate kidney injury in IgAN.     

PPE protein (Rv3425) from DNA segment RD11 of Mycobacterium tuberculosis: a potential B-cell antigen used for serological diagnosis to distinguish vaccinated controls from tuberculosis patients

Proteins encoded by a 9.5-kb DNA segment, termed the region of difference (RD), of Mycobacterium tuberculosis have been demonstrated to be important in bacterial virulence, vaccine development and the design of diagnostic reagents. This study evaluated the immunogenic properties of Rv3425, a member of the PPE family of proteins, encoded by an open reading frame found in RD11 of M. tuberculosis, in comparison with two other well-known antigens, the early secreted antigen target 6 (ESAT-6) and the 10-kDa culture filtrate protein (CFP-10). RT-PCR demonstrated that Rv3425 mRNA is expressed in liquid culture by M. tuberculosis H37Rv. When tested in a conventional ELISA in the form of a His-tagged recombinant protein, Rv3425 revealed a statistically significant antigenic distinction between healthy bacille Calmette-Guérin (BCG)-vaccinated controls and tuberculosis (TB) patients (p <0.0001). The anti-IgG response to recombinant Rv3425 was almost equal to that for CFP-10, and was higher than that for ESAT-6. The results highlight the immunosensitive and immunospecific nature of Rv3425, which shows promise for use in the serodiagnosis of TB.