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. 2022 Jun 25;10(7):1019.
doi: 10.3390/vaccines10071019.

In Silico Designed Multi-Epitope Immunogen "Tpme-VAC/LGCM-2022" May Induce Both Cellular and Humoral Immunity against Treponema pallidum Infection

Lucas Gabriel Rodrigues Gomes  1 , Thaís Cristina Vilela Rodrigues  1 , Arun Kumar Jaiswal  1 , Roselane Gonçalves Santos  1 , Rodrigo Bentes Kato  1 , Debmalya Barh  1   2 , Khalid J Alzahrani  3 , Hamsa Jameel Banjer  3 , Siomar de Castro Soares  4 , Vasco Azevedo  1 , Sandeep Tiwari  1
Affiliations

In Silico Designed Multi-Epitope Immunogen "Tpme-VAC/LGCM-2022" May Induce Both Cellular and Humoral Immunity against Treponema pallidum Infection

Lucas Gabriel Rodrigues Gomes et al. Vaccines (Basel). .

Abstract

Syphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum, has seen a resurgence over the past years. T. pallidum is capable of early dissemination and immune evasion, and the disease continues to be a global healthcare burden. The purpose of this study was to design a multi-epitope immunogen through an immunoinformatics-based approach. Multi-epitope immunogens constitute carefully selected epitopes belonging to conserved and essential bacterial proteins. Several physico-chemical characteristics, such as antigenicity, allergenicity, and stability, were determined. Further, molecular docking and dynamics simulations were performed, ensuring binding affinity and stability between the immunogen and TLR-2. An in silico cloning was performed using the pET-28a(+) vector and codon adaptation for E. coli. Finally, an in silico immune simulation was performed. The in silico predictions obtained in this work indicate that this construct would be capable of inducing the requisite immune response to elicit protection against T. pallidum. Through this methodology we have designed a promising potential vaccine candidate for syphilis, namely Tpme-VAC/LGCM-2022. However, it is necessary to validate these findings in in vitro and in vivo assays.

Keywords: Treponema pallidum; chimeric multi-epitope vaccine; immunoinformatics; sexually transmitted infection; syphilis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Multi-epitope immunogen (Tpme-VAC/LGCM-2022) construct with highlighted peptide linkers and epitopes. Sequence length is 558 amino acid residues. (B) Three-dimensional structure modelling of the chimeric protein after refinement by GalaxyRefiner. (C) Ramachandran plot for the model after refinement, showing 94.9% residues in most favored regions and 0.2% in disallowed regions.
Figure 2
Figure 2
Molecular docking of the Tpme-VAC/LGCM-2022 with the TLR-2 receptor structure representing the interaction with the lowest energy score. 3D structure of the complex. In green, the chimeric protein, and purple is the TLR-2. 3D structure of the complex, highlighting 2D representation of the interactions between TLR 2 and the chimeric protein. The figure represents the residues of the chimeric protein (Chain-B) and TLR2 receptor (Chain-A) with hydrogen bonds (green dotted lines). The residues involved in hydrophobic interactions are shown (Red).
Figure 3
Figure 3
Molecular dynamics simulation plots for the Tpme-VAC/LGCM-2022-TLR2 complex. (A) The temperature plot shows that the temperature of the system reaches over 300 K, and fluctuates around 300 K throughout the equilibration phase (1000 ps). (B) The pressure plot displays pressure fluctuation during the equilibration phase (1000 ps), with an average pressure of 0.5 bar. (C) RMSD plot of the receptor-ligand complex shows no significant deviation, indicating a stable interaction. (D) RMSF plot shows mild fluctuations of about 0.5 nm and higher peaks with an RMSF value of 2, due to the highly flexible loop regions in the complex.
Figure 4
Figure 4
In silico cloning. Reverse translated sequence of the Tpme-VAC/LGCM-2022 protein insert represented in red between the BlpI and BamHI restriction sites. Vector is represented in black.
Figure 5
Figure 5
Immuno simulation results of the Tpme-VAC/LGCM-2022 regarding: (A) B cells population per mm3 (B) PLB cell population per mm3. (C) Immunoglobulin production. (D) Helper T-cell population per state. (E) I Helper T-cell differentiation. (F) Cytotoxic T-cell population. (G) Cytotoxic T-cell population per state. (H) Cytokine production.
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