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Effect of oral immunization with recombinant urease on murine Helicobacter felis gastritis
1Vaccine Delivery Research Section, OraVax Inc., Cambridge, Massachusetts 02139.
Abstract:
The ability of oral immunization to interfere with the establishment of infection with Helicobacter felis was examined. Groups of Swiss Webster mice were immunized orally with 250 micrograms of Helicobacter pylori recombinant urease (rUrease) and 10 micrograms of cholera toxin (CT) adjuvant, 1 mg of H. felis sonicate antigens and CT, or phosphate-buffered saline (PBS) and CT. Oral immunization with rUrease resulted in markedly elevated serum immunoglobulin G (IgG), serum IgA, and intestinal IgA antibody responses. Challenge with live H. felis further stimulated the urease-specific intestinal IgA and serum IgG and IgA antibody levels in mice previously immunized with rUrease but activated primarily the serum IgG compartment of PBS-treated and H. felis-immunized mice. Intestinal IgA and serum IgG and IgA anti-urease antibody responses were highest in rUrease-immunized mice at the termination of the experiment. Mice immunized with rUrease were significantly protected (P < or = 0.0476) against infection when challenged with H. felis 2 or 6 weeks post-oral immunization in comparison with PBS-treated mice. Whereas H. felis-infected mice displayed multifocal gastric mucosal lymphoid follicles consisting of CD45R+ B cells surrounded by clusters of Thy1.2+ T cells, gastric tissue from rUrease-immunized mice contained few CD45R+ B cells and infrequent mucosal follicles. These observations show that oral immunization with rUrease confers protection against H. felis infection and suggest that gastric tissue may function as an effector organ of the mucosal immune system which reflects the extent of local antigenic stimulation.
Insights
Oral immunization with Helicobacter pylori recombinant urease (rUrease) protected mice against Helicobacter felis infection. This study highlights the potential of oral vaccination strategies for preventing gastric infections.
Area of Science:
- Immunology
- Gastroenterology
- Vaccinology
Background:
- Helicobacter felis infection establishes in the gastric mucosa.
- Oral immunization is a potential strategy for preventing gastrointestinal infections.
Purpose of the Study:
- To evaluate the efficacy of oral immunization with Helicobacter pylori recombinant urease (rUrease) in preventing Helicobacter felis infection in mice.
Main Methods:
- Mice were orally immunized with rUrease, H. felis sonicate antigens, or PBS, all with cholera toxin (CT) adjuvant.
- Mice were challenged with live H. felis.
- Serum and intestinal antibody responses (IgG, IgA) were measured.
- Gastric tissue histology was analyzed.
Main Results:
- Oral rUrease immunization induced significant serum and intestinal antibody responses.
- rUrease-immunized mice showed significant protection against H. felis challenge.
- Histological analysis revealed reduced gastric lymphoid follicles in rUrease-immunized mice.
Conclusions:
- Oral immunization with rUrease confers protection against H. felis infection.
- Gastric tissue may act as an effector organ in mucosal immunity.