Unveiling potential Helicobacter pylori vaccine candidates: A comprehensive multi-epitope approach

Helicobacter pylori is a pathogen known to cause persistent inflammation, leading to a wide spectrum of gastrointestinal diseases and gastric lesions. The chronic nature of this infection critically depends on host immune recognition and antigen presentation mechanisms, particularly those mediated by the major histocompatibility complex (MHC), a cluster of genes encoding cell-surfaces proteins that enable the immune system to detect and respond to foreign antigens. In this study, computational approaches were employed to identify and evaluate potential H. pylori targets for vaccine development, with a particular focus on antigenic and immunogenic epitopes associated with MHC class I and II molecules. We analyzed 12 complete genome strains of H. pylori, associated with different gastrointestinal diseases, encompassing a total of 30,775 predicted proteins. All data and predictions were integrated into a relational database, enabling systematic screening for extracellular or outer membrane epitopes that are both antigenic and safe. This process led to the identification of 27 candidate epitopes. To further characterize their immunological potential, molecular dynamics simulations were employed to evaluate the binding affinity between the predicted epitopes and MHC molecules. Multi-epitope complexes comprising B cells, CD4⁺ T cells, and CD8⁺ T cells, were ranked based on their binding affinity values. Among these, HPpep500, HPpep386, and HPpep283 emerged as promising candidates for subsequent in vitro and in vivo validation in the context of vaccine development. Overall, this study provides valuable insights into the rational design of an effective H. pylori vaccine.