Abstract
Syphilis, a sexually transmitted infection, is a deadly disease caused by Treponema pallidum. It is a Gram-negative spirochete that can infect nearly every organ of the human body. It can be transmitted both sexually and perinatally. Since syphilis is the second most fatal sexually transmitted disease after AIDS, an efficient vaccine candidate is needed to establish long-term protection against infections by T. pallidum. This study used reverse-vaccinology-based immunoinformatic pathway subtractive proteomics to find the best antigenic proteins for multi-epitope vaccine production. Six essential virulent and antigenic proteins were identified, including the membrane lipoprotein TpN32 (UniProt ID: O07950), DNA translocase FtsK (UniProt ID: O83964), Protein Soj homolog (UniProt ID: O83296), site-determining protein (UniProt ID: F7IVD2), ABC transporter, ATP-binding protein (UniProt ID: O83930), and Sugar ABC superfamily ATP-binding cassette transporter, ABC protein (UniProt ID: O83782). We found that the multiepitope subunit vaccine consisting of 4 CTL, 4 HTL, and 11 B-cell epitopes mixed with the adjuvant TLR-2 agonist ESAT6 has potent antigenic characteristics and does not induce an allergic response. Before being docked at Toll-like receptors 2 and 4, the developed vaccine was modeled, improved, and validated. Docking studies revealed significant binding interactions, whereas molecular dynamics simulations demonstrated its stability. Furthermore, the immune system simulation indicated significant and long-lasting immunological responses. The vaccine was then reverse-transcribed into a DNA sequence and cloned into the pET28a (+) vector to validate translational activity as well as the microbial production process. The vaccine developed in this study requires further scientific consensus before it can be used against T. pallidum to confirm its safety and efficacy.
Funder
Deanship of Scientific Research of King Khalid University
Princess Nourah bint Abdulrahman University Researchers Supporting Project
Subject
Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology
Reference88 articles.
1. A point mutation associated with bacterial macrolide resistance is present in both 23S rRNA genes of an erythromycin-resistant Treponema pallidum clinical isolate;Stamm;Antimicrob. Agents Chemother.,2000
2. Complete genome sequence of Treponema pallidum, the syphilis spirochete;Fraser;Science,1998
3. Matějková, P., Strouhal, M., Šmajs, D., Norris, S.J., Palzkill, T., Petrosino, J.F., Sodergren, E., Norton, J.E., Singh, J., and Richmond, T.A. (2008). Complete genome sequence of Treponema pallidum ssp. Pallidum strain SS14 determined with oligonucleotide arrays. BMC Microbiol., 8.
4. Complete genome sequence and annotation of the Treponema pallidum subsp. pallidum Chicago strain;Giacani;J. Bacteriol. Res.,2010
5. Baron, S. (2022, September 02). Medical Microbiology, Available online: https://pubmed.ncbi.nlm.nih.gov/21413252/.
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