Volume 116, Issue 4, Pages 804-812 (April 1999) Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori–infected adults  Pierre Michetti, Christianna Kreiss, Karen L. Kotloff, Nadine Porta, José–Luis Blanco, Daniel Bachmann, Maribelle Herranz, Pierre F. Saldinger, Irène Corthésy–Theulaz, Geneviève Losonsky, Richard Nichols, Joseph Simon, Manfred Stolte, Samuel Ackerman, Thomas P. Monath, André L. Blum  Gastroenterology  Volume 116, Issue 4, Pages 804-812 (April 1999) DOI: 10.1016/S0016-5085(99)70063-6 Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 1 Immunization-induced diarrhea occurred in 16 of 24 volunteers (66%). The frequency and severity of this side effect decreased with subsequent doses but were not influenced by the dose of rUrease. Mean number of stools of each study for each group is represented. ♢, Placebo; □, LT; ○, 20 mg rUrease; ▵, 60 mg rUrease; ▿, 180 mg rUrease. Gastroenterology 1999 116, 804-812DOI: (10.1016/S0016-5085(99)70063-6) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 2 Increased doses of rUrease induced increased specific serum IgA responses. Fold increases of postimmunization end point dilution ELISA values are plotted against the dose of rUrease administered orally to the volunteers (mean ± SEM). Wilcoxon rank sum tests were used to determine P values. Gastroenterology 1999 116, 804-812DOI: (10.1016/S0016-5085(99)70063-6) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 3 A significant antiurease IgA ASC response was observed in peripheral blood of volunteers exposed to all rUrease doses (*P = 0.03, Wilcoxon rank sum). Means ± SEM of postimmunization antiurease IgA-producing ASCs (▩) and IgG-producing ASCs (□) are represented. Pooled rUrease refers to combined results of groups 1–3 (n = 14). Volunteers exposed to 10 μg LT on day 1 (circles) tended to develop higher ASC responses than volunteers exposed to 5 μg LT (squares), but the differences did not reach statistical significance. Gastroenterology 1999 116, 804-812DOI: (10.1016/S0016-5085(99)70063-6) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 4 A significant LT-specific IgA ASC response was observed in peripheral blood of volunteers exposed to LT (*P = 0.05 vs. placebo IgA ASC; **P = 0.02 vs. placebo IgG ASC, Wilcoxon rank sum). Means ± SEM of postimmunization anti-LT IgA-producing ASCs (▩) and IgG-producing ASCs (□) are represented. Pooled rUrease refers to combined results of groups 1–3. Gastroenterology 1999 116, 804-812DOI: (10.1016/S0016-5085(99)70063-6) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 5 An immunization-induced decrease in gastric H. pylori density was observed only in group 3 (P = 0.043, paired t test) or when all rUrease-immunized groups were considered globally (*P = 0.032). (A) rUrease and (B) placebo/LT. No change occurred in the placebo and LT groups over time. Median colony-forming units (CFU) of 4 biopsy specimens (2 antrum and 2 corpus) in each volunteer at baseline (pre) and postimmunization (post) are represented. Open symbols refer to volunteers exposed to 10 μg LT on day 1 (see Materials and Methods for details). (A) ■ and □, 20 mg rUrease + LT; ▴ and ▵, 60 mg rUrease + LT; ● and ○, 180 mg rUrease. (B) ● and ○, placebo + LT; ■ and 2, placebo. Gastroenterology 1999 116, 804-812DOI: (10.1016/S0016-5085(99)70063-6) Copyright © 1999 American Gastroenterological Association Terms and Conditions