Pan-Genome-Assisted Computational Design of a Multi-Epitopes-Based Vaccine Candidate against Helicobacter cinaedi

Abstract

Helicobacter cinaedi is a Gram-negative bacterium from the family Helicobacteraceae and genus Helicobacter. The pathogen is a causative agent of gastroenteritis, cellulitis, and bacteremia. The increasing antibiotic resistance pattern of the pathogen prompts the efforts to develop a vaccine to prevent dissemination of the bacteria and stop the spread of antibiotic resistance (AR) determinants. Herein, a pan-genome analysis of the pathogen strains was performed to shed light on its core genome and its exploration for potential vaccine targets. In total, four vaccine candidates (TonB dependent receptor, flagellar hook protein FlgE, Hcp family type VI secretion system effector, flagellar motor protein MotB) were identified as promising vaccine candidates and subsequently subjected to an epitopes’ mapping phase. These vaccine candidates are part of the pathogen core genome: they are essential, localized at the pathogen surface, and are antigenic. Immunoinformatics was further applied on the selected vaccine proteins to predict potential antigenic, non-allergic, non-toxic, virulent, and DRB*0101 epitopes. The selected epitopes were then fused using linkers to structure a multi-epitopes’ vaccine construct. Molecular docking simulations were conducted to determine a designed vaccine binding stability with TLR5 innate immune receptor. Further, binding free energy by MMGB/PBSA and WaterSwap was employed to examine atomic level interaction energies. The designed vaccine also stimulated strong humoral and cellular immune responses as well as interferon and cytokines’ production. In a nutshell, the designed vaccine is promising in terms of immune responses’ stimulation and could be an ideal candidate for experimental analysis due to favorable physicochemical properties.

Helicobacter cinaedi bacterium association with atherosclerosis and other diseases

“…Recently, a paper has been published reporting computer modeling of a vaccine against H. cinaedi ( Ismail et al, 2022 ). This is the first project of a preventive strategy whose action is directed specifically at this microorganism.…”

Interactions between toll‐like receptors signaling pathway and gut microbiota in host homeostasis

“…52 Recently, flagellin has been developed as an adjuvant to vaccines, and a molecular approach to docking vaccines to TLR5 was used to determine the best vaccine pose. 53,54 In summary, TLR5 plays a nonredundant role in generating antiflagellin antibody responses that regulate intestinal microbial composition and motility. causing Reg3g expression and restoration of colonization resistance against vancomycin-resistant Enterococcus.…”

“…In some cases, bacteria evade TLR5 sensing and recognition by downregulating flagellin expression or mutating flagellin molecules 52 . Recently, flagellin has been developed as an adjuvant to vaccines, and a molecular approach to docking vaccines to TLR5 was used to determine the best vaccine pose 53,54 . In summary, TLR5 plays a nonredundant role in generating antiflagellin antibody responses that regulate intestinal microbial composition and motility.…”

Targeted Protein-Specific Multi-Epitope-Based Vaccine Designing against Human Cytomegalovirus by Using Immunoinformatics Approaches

“…Reverse vaccinology and computational vaccine designing are time saving when compared to conventional approaches of vaccine development [ 25 , 26 ]. These approaches have been widely used to evaluate target-protein-specific and proteome-wide, effective, safe, and stable vaccine candidates [ 27 , 28 , 29 ].…”