Designing an efficient multi-epitope oral vaccine against Helicobacter pylori using immunoinformatics and structural vaccinology approaches

Abstract

Helicobacter pylori is the cunning bacterium that can live in the stomachs of many people without any symptoms, but gradually can lead to gastric cancer. Due to various obstacles, which are related to anti-H. pylori antibiotic therapy, recently developing an anti-H. pylori vaccine has attracted more attention. In this study, different immunoinformatics and computational vaccinology approaches were employed to design an efficient multi-epitope oral vaccine against H. pylori. Our multi-epitope vaccine is composed of heat labile enterotoxin IIc B (LT-IIc) that is used as a mucosal adjuvant to enhance vaccine immunogenicity for oral immunization, cartilage oligomeric matrix protein (COMP) to increase vaccine stability in acidic pH of gut, one experimentally protective antigen, OipA, and two hypothetical protective antigens, HP0487 and HP0906, and "CTGKSC" peptide motif that target epithelial microfold cells (M cells) to enhance vaccine uptake from the gut barrier. All the aforesaid segments were joined to each other by proper linkers. The vaccine construct was modeled, validated, and refined by different programs to achieve a high-quality 3D structure. The resulting high-quality model was applied for conformational B-cell epitopes selection and docking analyses with a toll-like receptor 2 (TLR2). Moreover, molecular dynamics studies demonstrated that the protein-TLR2 docked model was stable during simulation time. We believe that our vaccine candidate can induce mucosal sIgA and IgG antibodies, and Th1/Th2/Th17-mediated protective immunity that are crucial for eradicating H. pylori infection. In sum, the computational results suggest that our newly designed vaccine could serve as a promising anti-H. pylori vaccine candidate.

Towards the first multi-epitope recombinant vaccine against Crimean-Congo hemorrhagic fever virus: A computer-aided vaccine design approach

“…Besides the various advantages of epitope-based vaccines, some weaknesses such as low immunogenicity and instability have faced the vaccine platform to serious challenge. Incorporating natural adjuvants in epitope-based vaccine construct can notably diminish these obstacles [19]. Hence, we merged the immunodominant epitopes with two natural adjuvants including CTxB and LT-IIc at N and C terminal using EAAAK linker.…”

“…Despite mentioned advantages of MEVs, poor immunogenicity is considered as a major drawback to development of MEVs [14][15][16]. To overcome the mentioned blind spot use of some natural protein-based adjuvants such as diphtheria toxin (DT), cholera toxin B-subunit (CTxB), heat-labile enterotoxin B subunit (LTB) and toll-like receptors (TLRs) ligands in final construct of proposed vaccines is suggested [17][18][19]. In the study, CTxB and LT-IIc were selected as protein adjuvants.…”

Harnessing self-assembled peptide nanoparticles in epitope vaccine design

“…Some limitations, namely instability, production complexity, low purity, and most importantly, the induction of an autoimmune response, are observed more frequently in protein-based subunit vaccines than in epitopebased subunit vaccines; therefore, epitope-based subunit vaccines are often preferred. They are composed of multiple individual antigenic epitopes from one or several pathogens (Azmi et al, 2014;Nezafat et al, 2017;Skwarczynski and Toth, 2011). These epitopes usually consist of B-cell epitopes, helper T-cell (Th) epitopes, and cytotoxic Tcell (CTL) epitopes.…”

“…Hence, these vaccines are considered efficient Toth, 2011, 2014). Based on the mentioned merits, many researchers, including our team, have worked extensively on the development of these types of vaccines (Farhadi et al, 2015;Hajighahramani et al, 2017;Mahmoodi et al, 2016;Nezafat et al, 2017;Nezafat et al, 2014;Nezafat et al, 2016;Shahbazi et al, 2016).…”

Helicobacter: Inflammation, immunology and vaccines

“…Successful vaccine development is a complex process, depending on many factors including choice of antigens, epitopes, adjuvants, delivery systems, and the administration route. No human trials of Helicobacter vaccines were published during the past year; however, several H. pylori articles were published on a variety of approaches, including using bioinformatics to improve the immunogenicity of H. pylori components . Several groups investigated Helicobacter vaccines using mouse models, however, very few tested their protective efficacy.…”