A Reverse Vaccinology and Immunoinformatic Approach for the Designing of a Novel mRNA Vaccine Against Stomach Cancer Targeting the Potent Pathogenic Proteins of Helicobacter pylori.

Helicobacter pylori infection of the stomach's epithelial cells is a significant risk factor for stomach cancer. Various H pylori proteins (CagA, GGT, NapA, PatA, urease, and VacA) were targeted to design 2 messenger RNA (mRNA) vaccines, V1 and V2, using bioinformatics tools. Physicochemical parameters, secondary and tertiary structure, molecular docking and dynamic simulation, codon optimization, and RNA structure prediction have also been estimated for these developed vaccines. Physicochemical analyses revealed that these developed vaccines are soluble (GRAVY < 0), basic (pI < 7), and stable (aliphatic index < 80). The secondary and tertiary structure of the vaccines demonstrated robustness. The docking with toll-like receptors (TLRs) revealed that the vaccines have a potential affinity for TLR-2 (V1: -1132.3 kJ/mol, V2: -1093.6 kJ/mol) and TLR-4 (V1: -1042.7 kJ/mol, V2: -1201.2 kJ/mol), and molecular dynamics simulations confirmed their dynamic stability. Structural analyses of V1 (-505.96 kcal/mol) and V2 (-634.92 kcal/mol) mRNA vaccines underscored their stability. In addition, the vaccine showed a considerable rise in the counts of B cells and extended activation of both T cells was also observed for the vaccines, suggesting the potential for long-lasting immunity, and offering enhanced protection against H pylori. These findings not only suggest potential long-lasting immunity against H pylori but also offer hope for the future of stomach cancer prevention. Notably, the study emphasizes the need for subsequent animal and human-based studies to confirm these promising results.