1. PETER MALFERTHEINER, VIOLA SCHULTZE,BERND ROSENKRANZ, STEFAN H.E. KAUFMANN TIMO ULRICHS,DEBORAH NOVICKI,FRANCESCO NORELLI,MARIO CONTORNI GASTROENTEROLOGY 2008;135:787–795 Safety and Immunogenicity of an Intramuscular Helicobacter pylori Vaccine in Noninfected Volunteers: A Phase I Study

2. INTRODUCTION Helicobacter pylori - gram-negative bacterium - colonizes the human gastric mucosa - most common chronic bacterial infections in human Western countries:10% ~60%, developing countries:about 100% acquired during childhood via intrafamily spread, persists throughout life

3. INTRODUCTION Combination therapy :PPI, antibiotics, and bismuth- containing compounds  항생제 저항성 증가, 재발 및 재감염 증가, 치료율 감 소 Vaccination using a variety of antigens  Ex) Urease : 세균 수 감소, 감염은 막지 못함

4. INTRODUCTION H. pylori 감염과 독성에 관여하는 세 가지 Ag - H. pylori vacuolating cytotoxin A (VacA) : epithelial injury and colonization - Cytotoxin-associated antigen (CagA): immunogenic protein translocated into gastric epithelial cells  more severe gastric disease and cancer - Neutrophil-activating protein (NAP) :activation of the neutrophils, monocytes, and mast cells  release of the proinflammatory mediators  promotion of the Th1-type immune responses

5. INTRODUCTION The purpose of this Phase I study - to assess the safety and immunogenicity of VacA, CagA, and NAP, with an aluminium hydroxide adjuvant, in healthy, H pylori-negative subjects.

6. MATERIALS AND METHODS Vaccine - Sterile purified recombinant VacA, CagA, and NAP adsorbed onto aluminium hydroxide (1 mg/mL), in 0.5 of isotonic buffer contained in prefilled syringes for IM injection into the deltoid muscle - Formulations: low (10 ug) or high (25 ug) doses of the 3 antigens, placebo(0.5 mg of aluminium hydroxide alone)

7. MATERIALS AND METHODS Subjects - Exclusion criteria: H. pylori 감염 또는 치료의 Hx, 최근 4 주내에 PPI, antibiotics, bismuth 로 치료한 Hx - Serologically negative for H. pylori at screening - Underwent a urea breath test at screening

8. phase I, randomized, controlled, single-blind, dose-ranging, and schedule-finding study 57 healthy adult (18–40yrs old) enrolled and randomly assigned to 1 of 7 groups

9. RESULTS

11. Figure 1. Serum IgG antibody titers against the CagA, NAP, and VacA(Monthly vaccinated group) Weekly vaccinated group  a strong antibody response to VacA after the second dose  a weaker response to NAP, CagA

12. 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.

13. Figure 3. Antigen-driven IFN- production by PBMC at different time

14. Figure 4. Antigen-specific antibody Response and antigen-driven IFN-production

15. CONCLUSION The intramuscular H. pylori vaccine demonstrated satisfactory safety and immunogenicity, produced antigen-specific T-cell memory, and, therefore, warrants further clinical study