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Helicobacter pylori vaccine development has progressed rapidly in animal models. Both H. pylori-associated pathogenesis and protective immunity are CD4+ T cell dependent, with no discernable phenotypic difference to distinguish pathogenic T cells from protective T cells. Functionally however, protective T cells promote enhanced inflammation upon H. pylori challenge. Additionally, only mouse models such as phagocyte oxidase- or IL-10-deficient mice that respond to H. pylori infection with intense gastritis are capable of demonstrating spontaneous eradication of the bacteria. These data, combined with recent descriptions of down-regulatory T cells in infected humans and mice, support an emerging model of H. pylori pathogenesis in which H. pylori induces inflammation that is limited by regulatory T cells in the stomach. Immunization therefore may succeed by activating T cells in peripheral lymph nodes that are capable of promoting qualitatively or quantitatively different inflammation when recruited to the stomach. Evidence in support of this model will be discussed.

To determine whether systemic immunization against Helicobacter pylori could be achieved with an adjuvant approved for human use, the efficacy of vaccination with Helicobacter antigen in combination with aluminum hydroxide (AlOH) was evaluated in a murine model of Helicobacter infection. Immunization with antigen and AlOH induced interleukin-5-secreting, antigen-specific T cells, and immunization with antigen and complete Freund's adjuvant induced interferon-gamma-secreting, antigen-specific T cells, as determined by ELISPOT assay. Both immune responses conferred protection after challenge with either H. pylori or H. felis, as confirmed by the complete absence of any bacteria, as assessed by both histology and culture of gastric biopsy samples. Protection was antibody independent, as demonstrated with antibody-deficient muMT mice (immunoglobulin-gene knockout mice), and CD4(+) spleen T cells from immunized mice were sufficient to transfer protective immunity to otherwise immunodeficient rag1(-/-) recipients. These results suggest an alternative and potentially more expeditious strategy for development of a human-use H. pylori vaccine.

Helicobacterpyloriinfection of the gastric mucosa is a significant cause of morbidity and mortality because of its etiologic role in symptomatic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Infection occurs in young children; therefore, a prophylactic vaccine would have to be administered within the first year of life, a period thought to be immunologically privileged. We investigated vaccine formulations administered by different routes to confer protective anti-H.pyloriimmunity in neonatal mice. Neonatal mice immunized with a single dose of vaccine in complete Freund's adjuvant (CFA) generated antigen-specific gamma interferon-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in numbers similar to those in immunized adult mice, while vaccine administered to neonates in incomplete Freund's adjuvant (IFA) induced such cells in reduced numbers compared to those in adult mice. Both IFA and CFA, however, provided partial protection from a challenge with infectiousH. pyloriwhen the vaccine was administered subcutaneously. Neonatal immunized mice also had reduced bacterial loads when immunized intraperitoneally with CFA. In all cases, protection was equivalent to that achieved when adult counterparts were immunized. These studies suggest that an efficacious vaccine might be successfully administered to very young children to prevent perinatal infection ofH.pylori.