Local Secretory Immunoglobulin A and Postimmunization Gastritis Correlate with Protection againstHelicobacter pyloriInfection after Oral Vaccination of Mice

Abstract

C57BL/6 mice were orally immunized with five weekly doses of 2 mg, 200 μg, or 2 μg of Helicobacter pylori (Sydney strain) whole-cell sonicate combined with cholera toxin. One week after the last vaccination, mice were challenged with 5 × 107CFU of live H. pylori three times at 2-day intervals. At 6 or 18 weeks after the challenge, mice were sacrificed and bacterial cultures and histological studies of the stomach were performed. Vaccination with 2 mg/session or 200 μg/session inhibited H. pylori colonization by 90 and 100%, respectively. These mice were considered protected. Lower levels of H. pylori-specific immunoglobulin A (IgA) were detected in fecal and saliva samples before challenge. However, a significant increase in IgA secretion in mucosal tissue and a higher labeling index for IgA-positive lumina of pyloric glands were noted in these mice in response to challenge and in a vaccine dose-dependent manner. In protected mice, however, severe gastritis characterized by marked infiltration of inflammation mononuclear cells was noted at 6 weeks after challenge, compared with the gastritis seen in unprotected mice or nonvaccinated, ordinarily infected mice. Marked expression of gamma interferon mRNA was detected in the stomach of all protected mice, and 50% of these mice expressed interleukin 4 (IL-4) or IL-5 mRNA. Our findings suggest that local secretory IgA antibody and severe postimmunization gastritis correlate well with protection of mice against H. pylori infection.

Protection Against Helicobacter pylori Infection in Mongolian Gerbil by Intragastric or Intramuscular Administration of H. pylori Multicomponent Vaccine

“…On the other hand, gerbils immunized with the LT R72DITH adjuvant vaccine exhibited lower titers of serum IgG but comparatively effective immune protection. These results indicated that the other immune mechanisms such as mucosal sIgA responses could be more important than the serum IgG response in immune protection against H. pylori infection, which is consistent with previous reports [6,49]. Due to the limitations of reagents for analysis of immune effector mechanisms in the Mongolian gerbil model, we could not pursue this study on mucosal sIgA response and other humoral immunity further.…”

Influence of age and duration of infection on bacterial load and immune responses to Helicobacter pylori infection in a murine model

“…All mice from the groups 1-3 were infected with ~ 10 7 colony forming units (CFU) of H. pylori (SS 1) as described previously [12]. Eight mice from each group were sacrificed at 1, 2, 4 and 8 weeks after infection except for group 1.…”

“…Histological examination (haematoxylin and eosin staining) was performed in a blinded fashion independently by two examiners. Because gastric specimens of infant mice were too small to evaluate the extent of inflammation, only the intensity of inflammation was scored on a scale of 0-3 as described previously [12]: grade 0, rare inflammatory cells; grade 1, mild; grade 2, moderate; and grade 3, severe inflammation with marked inflammatory cell infiltration.…”

“…Serum samples were tested by ELISA, using plates coated with the bacterial whole-cell lysates [12]. Biotinylated antimouse immunoglobulin (Ig) G or IgA (Zymed Laboratories Inc., San Francisco, CA, USA) was used as the secondary antibody.…”

Oral Vaccination Against Helicobacter pylori with Recombinant Cholera Toxin B‐Subunit

“…This step is thought to play an important role in steady induction of mucosal immunization. Similarly, Goto et al demonstrated that the high level of IgA observed in the stomach of mice vaccinated orally protects against infection [17].…”