Therapeutic Oral Vaccination Induces Mucosal Immune Response Sufficient to Eliminate Long‐Term Helicobacter pylori Infection

Abstract

We examined the efficacy of therapeutic oral vaccination using Helicobacter pylori-whole cell sonicate and cholera toxin (CT) in mice persistently infected with H. pylori. Efficacy was determined by bacterial culture and microscopic examination of gastric tissues for the persistence of bacteria at 6 weeks after the last vaccination. Vaccination of H. pylori-whole cell sonicate combined with CT eradicated bacteria in 10/16 mice (62.5%). Interestingly, oral vaccination with CT alone also eliminated the bacteria in 8/17 mice (47.1%). However, a therapeutic intraperitoneally administered vaccine failed to eradicate H. pylori from the stomach (1/17 mice, 5.9%). Identification of the type of immunity involved in the eradication process showed that oral vaccination enhanced the antigen-specific IgA in the feces and saliva. The efficacy of eradication of H. pylori correlated well with increases in IgA secretion in mucosal tissue and a higher labeling index of IgA-positive lumina of pyloric glands. Moreover, the expression of IL-4 mRNA in the stomach of mice with eradicated bacteria was higher than in the uneradicated group. Our results suggest that the efficacy of vaccination depends on the mucosal IgA response in the gastrointestinal tract against H. pylori via Th2 cell activation and that therapeutic oral vaccination induces a mucosal immune response sufficient to eradicate long-term infection with H. pylori.

Effects of a Th1- versus a Th2-biased immune response in protection against Helicobacter pylori challenge in mice

“…However, the mice were not challenged in that study and thus, the protective role of Th1 vs. Th2-type immunity was not defined. An H. pylori sonicate containing LPS, with either CT or heat-labile enterotoxin (LT), has normally been thought to induce Th2 immunity and reduce bacterial load in H. pylori vaccine studies [8,19,28]. However, in our study, we observed no reduction in bacterial load with a Th2 inducing, LPS−/CT vaccine (Fig.…”

“…This observation prompted early vaccine research to focus on the induction of T helper type 2 (Th2) immunity, since it was suspected that Th1 immunity prevented clearance from the host. Though some work supported this hypothesis [8], most studies suggest that in fact a strong Th1 biased environment, including increased gastritis, may be necessary for protection and clearance [13][14][15]. H. pylori vaccine studies using IL-4 knockout and B cell deficient mice have further supported this hypothesis, demonstrating that neither IL-4 nor antibody production (Th2 responses) are necessary for protection [13,16].…”

“…Typically, H. pylori infection persists throughout the life of the host despite the presence of a robust immune response [4,5]. In mice, vaccines have been developed that significantly reduce bacterial load, resulting in at least partial protection [6][7][8][9]. However, the immunological mechanisms that confer protection are not well understood.…”

Construction of expression systems forflaAandflaBgenes ofHelicobacter pyloriand determination of immunoreactivity and antigenicity of recombinant proteins

“…So far, no vaccine preventing H pylori infection has been commercially available. The majority of studies attempting to produce a vaccine have focused on urease enzyme, heat shock protein, and vacuolating cytotoxin [35,[48][49][50] , but rarely on H pylori flagellin. H pylori flagellin is composed of two subunits, named as FlaA with 53KDa and FlaB with 54 KDa respectively.…”

Evaluation of Therapeutic Efficacy of Adjuvant Helicobacter pylori Whole Cell Sonicate in Mice with Chronic H. pylori Infection

“…On the other hand, oral or parenteral immunization using H. pylori whole cell sonicate (WCS) or a recombinant urease seem to be effective in preventing subsequent H. pylori infection, as demonstrated in a series of studies seeking an alternative to antibiotic therapy. Goto et al (9) reported that H. pylori WCS combined with cholera toxin (CT) effectively prevented subsequent infection by H. pylori, and Ikewaki et al (14) described the efficacy of the same formula in reducing the number of colonizing bacteria. Furthermore, Guy et al (11,12) revealed that parenteral immunization with H. pylori urease plus certain adjuvants was effective against H. pylori infection when given prophylactically as well as for therapeutic purposes.…”