Helicobacter pylori (H. pylori) is the most common chronic bacterial infection, affecting half of the world’s population, and the main cause of gastric cancer. Once H. pylori has colonized its niche in the gastric mucosa, it can persist for decades, inducing a mostly asymptomatic, chronic inflammation that can further lead to the development of gastric and duodenal ulcers, mucosa-associated lymphoid tissue lymphoma, and finally result in gastric adenocarcinoma. Standard-of-care for H. pylori is still antibiotic combination therapy. However, treatment of H. pylori infection is hampered by rising antimicrobial resistance. The development of an efficacious mucosal vaccine is a valid alternative and must aim at inducing strong mucosal immunity to prevent transmission. Thus, the main goal of the project is to develop innovative delivery systems for an H. pylori mucosal vaccine to target antigen and adjuvant to mucosal antigen-presenting cells in the gastrointestinal tract. With this approach, we will improve mucosal vaccine design to finally induce mucosal immune responses required for long-term protection.