Helicobacter pylori overcomes natural immunity in repeated infections

Billions of humans in the world are infected with Helicobacter pylori 1. While H. pylori infection typically leads to lifelong asymptomatic colonization of the stomach, 10% of infections result in peptic ulcers, 1–5% of infections result in gastric cancer, and more rarely, infection leads to mucosa‐associated lymphoid tissue (MALT) lymphoma 1, 2. Treatment of H. pylori‐induced gastritis with antibiotics is effective 3. However, recurrence after treatment does occur 4. This could be due to failed eradication or reinfection. Our aim was to assess whether H. pylori infection in humans produces an immune response protective against future reinfection. Anti‐H. pylori antibodies are present in chronically infected persons, but fail to clear the infection 5. However, the protective role of natural immune responses to H. pylori has not previously been tested experimentally in humans. To assess whether H. pylori could overcome natural immunity, we eradicated the asymptomatic H. pylori infection in otherwise healthy subjects and then rechallenged them with their own strain of H. pylori. We assumed immunity would be maximal against an individual's own strain and would lead to the failure of reinfection attempts. Our findings have clinical significance in relation to strategies to combat H. pylori. They illuminate the significance of reinfection and inform vaccine development attempts, as an effective immune response is necessary for vaccination to work.