Abstract
Simple SummaryChlamydia trachomatis is the most common cause of blindness, ectopic pregnancy, and bacterial sexually transmitted infections. These diseases affect mostly young women but can also infect men and women of all ages. It is not difficult to treat, but it can lead to more significant health problems if left untreated. There is no licensed vaccine available for this pathogen at present. Hence, a vaccine that can control and prevent C. trachomatis infections is designed in this study by using different immuno-informatics approaches. However, the designed vaccine is the result of computational approaches; therefore, experimental validation is required to prove its effectiveness.Chlamydia trachomatis, a Gram-negative bacterium that infects the rectum, urethra, congenital sites, and columnar epithelium of the cervix. It is a major cause of preventable blindness, ectopic pregnancy, and bacterial sexually transmitted infections worldwide. There is currently no licensed multi-epitope vaccination available for this pathogen. This study used core proteomics, immuno-informatics, and subtractive proteomics approaches to identify the best antigenic candidates for the development of a multi-epitope-based vaccine (MEBV). These approaches resulted in six vaccine candidates: Type III secretion system translocon subunit CopD2, SctW family type III secretion system gatekeeper subunit CopN, SycD/LcrH family type III secretion system chaperone Scc2, CT847 family type III secretion system effector, hypothetical protein CTDEC_0668, and CHLPN 76kDa-like protein. A variety of immuno-informatics tools were used to predict B and T cell epitopes from vaccine candidate proteins. An in silico vaccine was developed using carefully selected epitopes (11 CTL, 2 HTL & 10 LBL) and then docked with the MHC molecules (MHC I & MHC II) and human TLR4. The vaccine was coupled with Cholera toxin subunit B (CTB) adjuvant to boost the immune response. Molecular dynamics (MD) simulations, molecular docking, and MMGBSA analysis were carried out to analyze the molecular interactions and binding affinity of MEBV with TLR4 and MHC molecules. To achieve the highest level of vaccine protein expression, the MEBV was cloned and reverse-translated in Escherichia coli. The highest level of expression was achieved, and a CAI score of 0.97 was reported. Further experimental validation of the MEBV is required to prove its efficacy. The vaccine developed will be useful in preventing infections caused by C. trachomatis.
Highlights
Chlamydia trachomatis is an ovoid-shaped, Gram-negative, and immobile bacterium commonly known as chlamydia [1,2]
Instead of large proteins or complete genomes, which are commonly employed in recombinant vaccine technology, the multi-epitope-based vaccine (MEBV) elicits immune responses based on small immunogenic sequences
The core proteome consists of 66,696 proteins. These proteins were subjected to Cluster Database at High Identity with Tolerance (CD-HIT) at an 80% threshold and 798 proteins were retrieved from 66,696 proteins by excluding paralog sequences
Summary
Chlamydia trachomatis is an ovoid-shaped, Gram-negative, and immobile bacterium commonly known as chlamydia [1,2]. Vaccination is thought to be the most effective way to lower the prevalence of C. trachomatis infections. It would be far less expensive and have a higher impact on global trachomatis infection control than a screening program or antibiotic treatment. In the last half century, knowledge regarding multi-epitope-based vaccines (MEBV) has become a thirst of the researchers who are willing and capable of designing vaccines in a short time with a small budget to meet global health challenges worldwide [21,22,23,24,25]. The clustered sequences were examined for the presence/absence of proteins in all input genomes and core protein sequences shared by all proteomes were considered for vaccine designing. These conserved sequences are attractive candidates for broad-spectrum vaccine design [34]
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