Identification and evaluation of the novel immunodominant antigen Rv2351c from Mycobacterium tuberculosis

Abstract

There is an urgent need for new immunodominant antigens to improve the diagnosis of tuberculosis (TB) and the efficacy of the TB vaccine to control the disease worldwide. In this study, we evaluated the diagnostic potential of a novel Mycobacterium tuberculosis (MTB)-specific antigen, Rv2351c, from region of difference (RD) 7 of the MTB genome, and investigated the potency of the vaccine by identifying its immunological function in human and animal immunological experiments. Twenty T-cell epitopes were identified using TEpredict and prediction tools from the Immune Epitope Database and Analysis Resource. A total of 159 subjects, including 61 patients with pulmonary TB, 38 patients with no TB and 55 healthy donors, were recruited and analyzed with an enzyme-linked immunospot (ELISpot) assay. The ELISpot assay using Rv2351c to detect TB infection, as compared with bacteriological tests as the gold standard, had a sensitivity and specificity of 61.4% (35/57) and 91.4% (85/93), respectively. The ELISpot assay using Rv2351c had a good conformance (κ=0.554) as compared with the bacteriological test. Rv2351c also elicited a potent cellular immune response with a high expression of cytokines (IFN-γ (4978±596.7 μg/mL) and IL-4 (68.3±15.5 μg/mL)) and a potent humoral immune response with a high concentration of IgG (1:2.2 × 106), IgG1 (1:4.5 × 105) and IgG2a (1:1.6 × 106) in immunized BALB/c mice. In addition, the ratio of IgG2a/IgG1 indicated that Rv2351c induced cellular immunity in the mice. The results of this study indicated that Rv2351c is an antigen with good immunogenicity that may potentially be used to develop diagnostic techniques and new TB vaccines.

IgY antibodies for the immunoprophylaxis and therapy of respiratory infections

“…116 The combination of TB with HIV/AIDS and the development of multidrug-resistant strains have increased the disease burden. 117 Immunotherapy might present a new option for treating drug-resistant TB strains, with promising outcomes and better quality of life for patients.- 118 Intramuscular immunization of Lohmann laying hens showed an increase of anti-MTBC IgY antibodies in egg yolk, with peak concentration at 4 weeks after immunization. The specific antibodies were persist 200 days after the last immunization.…”

A Multistage Antigen Complex Epera013 Promotes Efficient and Comprehensive Immune Responses in BALB/c Mice

“…Previously, we have evaluated the immunogenicity of several antigens from MTB, both in full-length and truncated modalities (T cell epitope focused regions). The results suggested that the antigens possessed high immunogenicity and may have promising effects on TB vaccine development [ 13 , 14 , 15 ]. On the basis of these efforts, we designed two multistage antigen complexes Epera013f and Epera013m, which comprised three full-length antigens EsxH, EsxB and Ag85B and two truncated antigens new RipD (nRipD) and new PPE18 (nPPE18), either as a protein mixture (Epera013m) or a fusion protein (Epera013f).…”

“…The frequently used T-cell epitope prediction tools include TEpredict, which is based on the data of HLA allele genotypic frequencies and the online tools of IEDB-AR database (Immune Epitope Database and Analysis Resource). Work by Wang X et al [ 14 ] suggested that a combined utilization of two T-cell epitope prediction tools might improve the accuracy and efficiency of the predicted epitopes and facilitate the advance of vaccine development.…”

Cloning, Expression and T Cell Epitope Prediction of Fbpa and FBPB Genes of Mycobacterium Tuberculosis Clinical Isolates

“…Indonesia has the second largest burden of TB cases in the world after India. In 2017, there were 425,089 TB cases in Indonesia, indicating a dramatic increase compared to the previous year of 360,565 cases with a mortality rate of 42 per 100,000 population (Wang et al, 2017; WHO 2018; Ministry of Indonesia Health 2018). The problem of preventing and controlling TB is very complex because the effective TB treatment and accurate diagnosis are not established yet (Guginno et al, 2015).…”