Prediction of a novel synthetic peptide vaccine against tuberculosis and validation of its immunogenicity

Abstract

Background

Tuberculosis (TB) is an infectious disease transmitted through the respiratory system that affects people worldwide. Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, has been shown to have highly variable protective efficacy in different populations and is ineffective at protecting adults. Therefore, the development of more effective TB vaccines is vital.

Methods

Three dominant antigens (ESAT6, CFP10, and MPT64) from the region of difference were selected for this study. Their physicochemical properties, spatial structures, and immune responses were evaluated using bioinformatics screening of dominant T cell and B cell epitopes. Three vaccine constructs were developed. After selecting the appropriate linkers, their physicochemical properties, spatial structures, and immune responses of the vaccines were evaluated, and molecular dynamics simulations were performed to test their ability to bind to major histocompatibility complex (MHC) receptors within 100 ns.

This process aimed to create highly antigenic vaccine constructs capable of eliciting an immune response. The effects of the vaccine constructs on the host immune response were assessed using enzyme-linked immunosorbent assays, flow cytometry, and hematoxylin and eosin staining.

Results

A novel peptide vaccine, designated ECM-64, was developed by screening six immunodominant peptides from three antigens and constructing independent T-epitope and B-epitope vaccines. Compared weith BCG-immunized mice, ECM-64-immunized mice exhibited a substantial augmentation in Th1/Th2 cytokine secretion and CD3⁺CD4⁺T and CD3⁺CD8⁻T lymphocyte counts. ECM-64-specific IgG and IgG1 antibodies were produced after immunization. The immunoinformatics findings were largely consistent with those obtained from the analysis of immunized mice.

Conclusion

ECM-64 is a promising multipeptide TB vaccine with the advantage of inducing high levels of Th1/Th2 cytokines, antibodies, and CD3⁺CD4⁺T and CD3⁺CD8⁻T lymphocytes in mice. This study also provides preliminary evidence that bioinformatic methods can be used to screen for dominant epitopes.

These findings lay the groundwork for the development of peptide-based TB vaccines.