Novel Chimeric Vaccine Candidate Development against Leptotrichia buccalis

Abstract

The misuse of antibiotics in our daily lives has led to the emergence of antimicrobial resistance. As a result, many antibiotics are becoming ineffective. This phenomenon is linked with high rates of mortality and morbidity. Therefore, new approaches are required to address this major health issue. Leptotrichia buccalis is a Gram-negative, rod-shaped bacterium which normally resides in the oral and vaginal cavities. It is an emerging bacterial pathogen which is developing new antibiotic-resistance mechanisms. No approved vaccine is available against this pathogen, which is a cause for growing concern. In this study, an in silico-based, multi-epitopes vaccine against this pathogen was designed by applying reverse vaccinology and immunoinformatic approaches. Of a total of 2193 predicted proteins, 294 were found to be redundant while 1899 were non-redundant. Among the non-redundant proteins, 6 were predicted to be present in the extracellular region, 12 in the periplasmic region and 23 in the outer-membrane region. Three proteins (trypsin-like peptidase domain-containing protein, sel1 repeat family protein and TrbI/VirB10 family protein) were predicted to be virulent and potential subunit vaccine targets. In the epitopes prediction phase, the three proteins were subjected to B- and T-cell epitope mapping; 19 epitopes were used for vaccine design. The vaccine construct was docked with MHC-I, MHC-II and TLR-4 immune receptors and only the top-ranked complex (based on global energy value) was selected in each case. The selected docked complexes were examined in a molecular dynamic simulation and binding free energies analysis in order to assess their intermolecular stability. It was observed that the vaccine binding mode with receptors was stable and that the system presented stable dynamics. The net binding free energy of complexes was in the range of −300 to −500 kcal/mol, indicating the formation of stable complexes. In conclusion, the data reported herein might help vaccinologists to formulate a chimeric vaccine against the aforementioned target pathogen.

Chimeric vaccine design against the conserved TonB-dependent receptor-like β-barrel domain from the outer membrane tbpA and hpuB proteins of Kingella kingae ATCC 23330

“…These regions are often more flexible and exhibit more conformational changes than the other parts of the protein ( Papaleo et al, 2016 ). Loop regions have immunogenic characteristics and are used in vaccine design for HIV ( Montero et al, 2008 ), Leptotricha buccalis ( Alshammari et al, 2022 ), and dengue virus ( Urakami et al, 2017 ). Previously, Ismail et al described fluctuations in the loop regions of the vaccine construct against Enterobacteriaceae, with loops inferred to adopt a stable conformation with increasing time, during the simulation ( Ismail et al, 2020 ).…”

A novel vaccine construct against Zika virus fever: insights from epitope-based vaccine discovery through molecular modeling and immunoinformatics approaches

“…This analysis aimed to determine the coverage of the shortlisted epitopes for alleles that represent the global population ( 24 ). The goal was to design a multiepitope vaccine that can target a large portion of the world population ( 25 ).…”

“…The physicochemical characteristics and “antigenicity, allergenicity, adhesion probability”, as well as the secondary structure parameters of the construct were analyzed ( 27 ). The final vaccine construct’s molecular weight, hydrophilicity, and theoretical and instability index were obtained using the Protparam tool from Expasy ( 25 ). To predict the 3D structure of the vaccine design, we utilized the Scratch predictor ( 28 ).…”

“…To investigate the interconnection between the vaccine model and receptor, a molecular docking analysis was conducted ( 35 ). TLR receptors play a crucial role in triggering cytokine production, which, in turn, activates the innate immune response ( 25 ). The ClusPro 2.0 ( 36 ) online tool was utilized for the analysis of docking ( 37 ).…”

Immunoinformatics assisted profiling of West Nile virus proteome to determine immunodominant epitopes for the development of next-generation multi-peptide vaccine

“…Molecular docking analysis is a computational-based analysis that is mainly used for binding interaction analysis between ligand and receptor molecules (Vaccine and immune cells receptors (38,39), In the molecular docking analysis phase immune cell receptor molecule, was selected as a receptor for the design of vaccine construct, and pdb structure of the Toll-like receptor-3 (TLR-3) was retrieved from protein data bank (pdb) (40) and prepare for docking with vaccine using UCSF chimaera tool (41), for molecular docking analysis cluspro 2.0 web tool was utilized (38), the target receptor TLR-3 plays a vital role in the immunogenicity in the pathogenesis of viral pathogenic species (42). Both the vaccine and receptor PDB files were uploaded to the cluspro 2.0 web server and submitted for docking analysis.…”