As the Cause of Stomach Ulcer has been Decoded, Scientist are striving for Vaccines.

Since ancient times, it was thought that painful stomach ulcers were caused by eating spicy foods or having an unhealthy diet. But since then, researchers have found that Helicobacter pylori, a common bacterium found in over 60% of the world’s population, was the real culprit behind most stomach ulcers and a high risk for stomach cancer.

Now scientists from the Ateneo de Manila University School of Science and Engineering’s Department of Biology are on the way to finding a vaccine to fight off the bacterium, possibly preventing stomach ulcers and lowering the risk for stomach cancer.

Ateneo biologists Demy Valerie Chacon, Kiana Alika Co, Daphne Noreen Enriquez, Aubrey Love Labarda, Reanne Eden Manongsong, and Edward Kevin Bragais used a cutting-edge approach called “immunoinformatics” that combines computer science with immunology to scan the genetic makeup of pathogens and predict which parts of them can trigger a strong immune response. By running thousands of gene sequences through these computational tools, researchers can narrow down the most promising vaccine targets much faster and at lower cost than through trial-and-error lab work alone.

The Ateneo biologists have identified key proteins produced by H. pylori those help it survive stomach acid, stick to the stomach lining, and evade the body’s natural immune system. Their analysis also identified parts of these proteins that are most likely to be safe, non-allergenic, and capable of activating protective immune cells.

The Research Study –

While their research findings are still preliminary and based on computer simulations, the next steps include laboratory testing to validate these predictions. To date, there are no approved vaccines against H. pylori despite ongoing tentative research in other laboratories around the world. However, if successful, the Ateneo research could pave the way for the first-ever H. pylori vaccine that could help guard against stomach ulcers and cancer.

Helicobacter pylori infects approximately half of the global population, leading to gastric and duodenal ulcers. Despite the availability of antibiotics, challenges such as patient reluctance, high treatment costs, and antibiotic resistance limit their effectiveness, making vaccination a promising alternative. This study used immunoinformatics to identify candidate epitopes for a multiepitope vaccine construct against H. pylori.

The protein variability server was utilized for conservation analysis. The epitopes were screened for antigenicity, allergenicity, toxicity, cross-reactivity, and population coverage. Selected epitopes were docked with their corresponding human leukocyte antigen (HLA) alleles, and thermodynamic quantities were determined. Five virulence factors, namely HopZ, SabA, HP-NAP, OipA, and urease were selected for their critical roles in bacterial adhesion, immune modulation, and stress survival.

Conservation analysis revealed a highly conserved protein sequence (Shannon index £ 0.1). The predicted epitopes had an IC50 value of £ 500 nM, indicating strong binding to the corresponding HLAs, with an estimated population coverage of more than 90% in the Southeast Asian region. The predicted epitopes were identified as probable nonallergens, nontoxic, and noncross-reactive (E value >1.0). Molecular docking analysis showed that the candidate epitopes could bind strongly and spontaneously with their corresponding HLA proteins, as evidenced by low negative Gibbs free energy (DG) values and dissociation constants (KD < 100 nM).

The epitopes predicted from the five virulence factors present promising candidates for future H. pylori vaccine design. Further in vitro and in vivo experiments are recommended to validate these preliminary findings.

Team Maverick