Helicobacter pylori vaccines: from bench to bedside—progress, challenges, and future directions

Helicobacter pylori ( H. pylori ) is a major human pathogen that colonizes the gastric mucosa and is a principal etiological agent of gastritis, peptic ulcer disease, and gastric cancer. Although antibiotic-based eradication regimens are available, their cost and the poor prognosis of established gastric cancer make vaccination an economically attractive and potentially more durable alternative. This narrative review synthesizes the literature on H. pylori pathogenesis, host protective immunity, and vaccine development, with particular attention to the human clinical trials reported since 1999 and with emphasis on preclinical work published since 2020. Rather than cataloguing candidate antigens, we organize the field into three interdependent tiers—classical approaches, emerging technologies, and the enabling adjuvant and delivery platforms on which both depend—and use this framework to examine why preclinical success has repeatedly failed to translate into clinical protection, and to identify the principal challenges now facing human H. pylori vaccine development. We conclude that the principal bottleneck is no longer antigen discovery but antigen delivery and immune programming at the gastric mucosa.