Volume 135, Issue 3, Pages 787-795 (September 2008) Safety and Immunogenicity of an Intramuscular Helicobacter pylori Vaccine in Noninfected Volunteers: A Phase I Study  Peter Malfertheiner, Viola Schultze, Bernd Rosenkranz, Stefan H.E. Kaufmann, Timo Ulrichs, Deborah Novicki, Francesco Norelli, Mario Contorni, Samuele Peppoloni, Duccio Berti, Daniela Tornese, Jitendra Ganju, Emanuela Palla, Rino Rappuoli, Bruce F. Scharschmidt, Giuseppe Del Giudice  Gastroenterology  Volume 135, Issue 3, Pages 787-795 (September 2008) DOI: 10.1053/j.gastro.2008.05.054 Copyright © 2008 AGA Institute Terms and Conditions

Figure 1 Serum IgG antibody titers against the CagA, NAP, and VacA in volunteers immunized (arrowheads) with the antigens at 10 μg/dose (☐, low dose) or 25 μg/dose (○, high dose) according to 2 monthly schedules (0, 1, 2 or 0, 1, 4), or with placebo (alum, *). Each dot represents the GMT at each time point ± 90% confidence intervals. Horizontal dotted lines represent the cut-off value for each ELISA. Starting from the first time point after the second immunization for NAP and VacA and the first time point after the third immunization for CagA, all points were significantly higher than placebo (P < .001). Gastroenterology 2008 135, 787-795DOI: (10.1053/j.gastro.2008.05.054) Copyright © 2008 AGA Institute Terms and Conditions

Figure 2 Percentage of individuals who seroconverted to 2 (left panels) or to all 3 antigens (right panels) after monthly immunizations (arrowheads) at each time point. Symbols are as in Figure 1. Seroconversion was prospectively defined as values below the EU cut-off levels before vaccination which became positive after vaccination, or when values above cut-off levels before vaccination increased ≥3-fold after vaccination. At visits after the third immunization all treatment groups were significantly higher than placebo (P < .001); there was no statistically significant difference between seroconversion rates in the high-dose (25 μg/dose) or low-dose (10 μg/dose) groups at any time point tested in each of the different immunization schedules. Gastroenterology 2008 135, 787-795DOI: (10.1053/j.gastro.2008.05.054) Copyright © 2008 AGA Institute Terms and Conditions

Figure 3 Antigen-driven IFN-γ production by PBMC at different time points before vaccination and 3 and 5 months after the first dose (☐, low dose; ○, high dose; *, placebo). Results are expressed as protein concentration in the supernatants (ng/mL). Each point represents the GMT per group per time point ± 90% confidence intervals. Gastroenterology 2008 135, 787-795DOI: (10.1053/j.gastro.2008.05.054) Copyright © 2008 AGA Institute Terms and Conditions

Figure 4 Antigen-specific antibody response (top panels; GMT ± 90% confidence intervals) and antigen-driven IFN-γ production (bottom panels; GMT ± 90% confidence intervals) at baseline (0), after 3 primary immunizations (p3), and before (prB) and after (poB) booster immunization 18–24 months after the primary immunization series. (☐, monthly 012 schedule; ■, monthly 014 schedule; ○, weekly schedule). Gastroenterology 2008 135, 787-795DOI: (10.1053/j.gastro.2008.05.054) Copyright © 2008 AGA Institute Terms and Conditions