A Novel Multi-Epitopic Peptide Vaccine Candidate Against Helicobacter pylori: In-Silico Identification, Design, Cloning and Validation Through Molecular Dynamics

Abstract

Helicobacter pylori is a highly potential pathogen to colonize in the human stomach. This bacterial strain is now alarming serious health concern all over the world. Combating through available drugs is a difficult task due to lack of appropriate common targets against genetically diverse strains. Therefore, the developments of effective targets vaccines require alternative strategies to eliminate the H. pylori infection. In this study, we developed a novel vaccine construct using B-cell derived T-cell epitopes from four target antigenic proteins (HpaA, FlaA, FlaB and Omp18), and found the induction of possible immune response using advanced immunoinformatics approaches. In order to boost immune system, we tagged adjuvant (50S ribosomal protein L7/L12) with a suitable linker at the N-terminus side of vaccine sequence. Protein-protein docking between human Toll like receptor 5 (TLR5) and vaccine construct help to predict the way of inductive signaling that leads to immune-response. The calculated negative score (− 151.4, + / − 8.7) of molecular docking complex signify the best binding interface. Molecular dynamics simulation studies confirmed the proper docking between TLR5 and vaccine candidate. Moreover, Normal mode analysis (NMA) calculates the molecular motion of the docking complex. The low eigenvalue (2.935e −05 ) indicates the stable and flexible molecular motion in the binding interaction side. Finally, in-silico cloning of vaccine candidate was performed using expression vector pET28b (+) with the optimized restriction sites.

Peptide-Based Vaccines for Tuberculosis

“…Therefore, enhancing host immune responses with TLR2 and TLR4 agonists may be the option for constructing an ideal peptide-based vaccine in future. At present, some TLR2 and TLR4 agonists have been used in peptide-based vaccines against infectious diseases, including TB, such as TLR2 agonists ESAT6 (144), phenol-soluble modulin a4 (PSMa4) (145), dipalmitoyl-S-glyceryl cysteine (Pam2Cys) (115,146), and PorB (147,148), TLR4 agonists RpfE (Rv2450c) (149), 50S ribosomal protein L7/L12 (RplL) (22,(150)(151)(152)(153)(154)(155), heparin binding hemagglutinin (HBHA) (156), cholera toxin subunit B (CTB) (157)(158)(159), and RS-09 (160,161). In addition, helper peptides and antimicrobial peptides are also used to construct peptide-based vaccines to enhance their immune effects, such as PADRE (148) (151) (156), Hsp70 (161), TR-433 (161), human bdefensin 1 (HBD-1) (162), HBD-2 (163), HBD-3 (19,(164)(165)(166)(167), and Griselimycin (84).…”

Molecular Docking Study of Nutmeg (Myristica Fragrans) Constituents as Anti-Skin Cancer Agents

“…As can be seen from the comparison of our RMSD with the RMSD as mentioned above, this research could continue using our validated docking protocol [31]. The RMSD below 2.0 Å indicates the formation of good quality docking method [32].…”

In-Silico Vaccine Design Based on a Novel Vaccine Candidate Against Infections Caused by Acinetobacter baumannii

“…Multi-epitope vaccines have an edge over classic vaccines due to their higher efficiency, fewer chances of cross-reactivity, cost-effectiveness, and ability to create biased immune responses (Sette et al 2001 ; Goumari et al 2019 ). Formerly, a plethora of multi-epitope vaccines has been conceived using computational tools against several bacterial infections such as Helicobacter pylori (Ghosh et al 2021 ), Klebsiella pneumoniae (Dar et al 2019 ), Pseudomonas aeruginosa (Solanki et al 2019 ), Vibrio cholerae (Nezafat et al 2016 ), Shigella spp. (Nosrati et al 2019 ), Brucella (Saadi et al 2017 ), Aeromonas hydrophilla (Bhattacharya et al 2020 ), Prostate cancer (Patra et al 2020 ) and many others.…”