Fusion peptide constructs from antigens of M. tuberculosis producing high T-cell mediated immune response

Abstract

Non availability of effective anti-TB vaccine impedes TB control which remains a crucial global health issue. A fusion molecule based on immunogenic antigens specific to different growth phases of Mycobacterium tuberculosis can enhance T-cell responses required for developing a potent vaccine. In this study, six antigens including EspC, TB10.4, HspX, PPE57, CFP21 and Rv1352 were selected for constructing EspC-TB10.4 (bifu25), TnCFP21-Rv1352 (bifu29), HspX-EspC-TB10.4 (trifu37), HspX-TnCFP21-Rv1352 (trifu44) and HspX-EspC-TB10.4-PPE57 (tetrafu56) fusion proteins. Th1-cell epitopes of EspC, PPE57 and Rv1352 antigens were predicted for the first time using different in silico tools. The fusion molecule tetrafu56, which consisted of antigens from both the replicating and the dormant stages of Mtb, induced a release of 397 pg/mL of IFN-γ from PBMCs of the active TB patients. This response was comparable to the response obtained with cocktail of the component antigens (396 pg/mL) as well as to the total of the responses obtained separately for each of its component antigens (388 pg/mL). However, PBMCs from healthy samples in response to tetrafu56 showed IFN-γ release of only 26.0 pg/mL Thus a previous exposure of PBMCs to Mtb antigens in TB plasma samples resulted in 15-fold increase in IFN-γ response to tetrafu56 as compared to the PBMCs from the healthy controls. Hence, most of the T-cell epitopes of the individual antigens seem to be available for T-cell interactions in the form of the fusion. Further investigation in animal models should substantiate the immune efficacy of the fusion molecule. Thus, the fusion tetrafu56 seems to be a potential candidate for developing an effective multistage vaccine against TB.

Re-Evaluating Human Cytomegalovirus Vaccine Design: Prediction of T Cell Epitopes

“…Other computational vaccine studies used alternative methods, including molecular docking and immunogenicity simulation, prediction of non-allergenicity, physicochemical properties of peptides, expression feasibility, and tertiary structure modeling of the vaccine construct [64,65,67]. By extension, comparable in silico approaches are being evaluated for Mycobacterium tuberculosis, Plasmodia species, and seasonal influenza variants [68][69][70][71]. In a recent novel approach targeting another Herpesviridae pathogen, a multivalent Epstein-Barr Virus (EBV) vaccine was constructed to include multiple humoral and CD8 T cell antigens of both lytic and latent proteins presented by common HLA class I alleles to enable global utility [72].…”

Synthesis and Anti‐Bacterial Evaluation of Novel Scaffolds Based on Bis‐Thiazole or bis‐1,3,4‐Thiadiazole Linked to Thieno[2,3‐b]Thiophene as New Hybrid Molecules

“…The compounds prevented the growth of the tested bacteria by diffusing into the agar media from the discs, (if susceptible) in the zone of inhibition, which is the vicinity of the disc. Zones of inhibition from every treatment were computed the next day [80] …”

Immunological effects of the PE/PPE family proteins of Mycobacterium tuberculosis and related vaccines

“…Their construction into a fusion protein can enable interaction with T cells and amplify the immune effect. This vaccine has been shown to induce high levels of protective IFN-γ (average = 397 pg/mL) from the PBMCs of patients with active pulmonary TB, but PBMCs from healthy adults were not sensitive to the vaccine and induced a low level of IFN-γ (average = 26.0 pg/mL) ( 137 ). Tetrafu56 (which incorporates PPE57) is a multiphase vaccine against TB composed of antigens from the active replication and resting stages of Mtb .…”