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Infection and Immunity, May 1999, p. 2531-2539, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Local Secretory Immunoglobulin A and Postimmunization Gastritis Correlate with Protection against Helicobacter pylori Infection after Oral Vaccination of Mice

Takayuki Goto,1 Akira Nishizono,2,* Toshio Fujioka,1 Junko Ikewaki,3 Kumato Mifune,3 and Masaru Nasu1

Second Department of Internal Medicine,1 Department of Infectious Disease Control,2 and Department of Microbiology,3 Oita Medical University, Hasama-machi, Oita, Japan

Received 19 August 1998/Returned for modification 10 November 1998/Accepted 20 January 1999

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 × 107 CFU 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.

* Corresponding author. Mailing address: Department of Infectious Disease Control, Oita Medical University, Idaigaoka 1-1, Hasama-machi, Oita 879-5593, Japan. Phone: 81-97-586-5701. Fax: 81-97-586-5719. E-mail: a24zono{at}oita-med.ac.jp.

Infection and Immunity, May 1999, p. 2531-2539, Vol. 67, No. 5
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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