Systemic Th1 immunization of mice against Helicobacter pylori infection with CpG oligodeoxynucleotides as adjuvants does not protect from infection but enhances gastritis.

Abstract

Recent reports have suggested that oral vaccination of mice against Helicobacter pylori is dependent on a Th1-mediated immune response. However, oral vaccination in mice neither induces sterilizing immunity nor leads to complete protection from disease. Therefore, in this study we investigated whether a systemic subcutaneous immunization against H. pylori by using CpG oligodeoxynucleotides as a Th1 adjuvant could achieve protection in a mouse model of H. pylori infection. CpG oligodeoxynucleotides are known for their ability to induce nearly entirely Th1-biased immune responses and may be approved for human use in future. Immunization of mice with H. pylori lysate and CpG induced a strong local and systemic Th1 immune response. Despite this strong Th1 response, mice were not protected from infection with H. pylori yet had a 10-fold reduction in the number of H. pylori in the gastric mucosa compared to nonimmunized mice. Of note, reduction of the bacterial density in immunized mice was accompanied by a significantly enhanced gastritis. Hence, systemic Th1 immunization of mice, even though being able to reduce the bacterial load in the stomach, is associated with aggravated pathology.