| Helicobacter pylori has been colonizing and evolving with man for over 100,000 years, adapting many mechanisms to evade host immunity and prevent clearance. Both humoral and cellular host immune responses to chronic H. pylori infection are strong and persistent however, they are not protective. Unlike most extracellular bacterial pathogens, research has demonstrated that T helper 1 (Th1) type immune responses may be necessary for protection against H. pylori infection. The mechanisms by which these protective Th1 lymphocyte responses confer protection are unknown. There is likely a complex interaction between H. pylori and host immunity that contributes to protective responses. The goal of this project was to better understand host immune responses following vaccination and their role in protection against H. pylori .H. pylori lipopolysaccharide (LPS) was previously thought to induce very little endotoxic activity and was not expected to elicit host immune responses. In this project, through vaccination with an LPS depleted cell sonicate, we demonstrated that H. pylori LPS does play a functional role in promoting host immunity, in particular induction of Th1 skewed protective responses. Thus, mice immunized with an LPS depleted H. pylori sonicate and cholera toxin (CT), a Th2 promoting adjuvant, showed no decrease in H. pylori bacterial load following oral challenge, despite vigorous host responses.Determining the optimal route of immunization to promote long-term memory responses is an important factor in the success of a vaccine, especially against a mucosal pathogen such as H. pylori. Thus, efficacy was evaluated for several immunization routes using both parenteral and mucosal immunizations. Significant decreases in H. pylori bacterial loads were seen in mice challenged three months after either five intramuscular immunizations (IM) or three oral immunizations followed by two intramuscular immunizations (Oral/IM). In addition to decreased bacterial loads, increases in interleukin 12, IgG1, and IgG2a were all detected after challenge in the IM and Oral/IM groups. Together, these studies demonstrate the role of H. pylori LPS as a virulence factor on host immunity and define immune responses that may be necessary for long-term protection against H. pylori infection. |
