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Safety and Immunogenicity of
an Intramuscular Helicobacter pylori Vaccine
in Noninfected Volunteers: A Phase I Study
P E T E R M A L F E R T H E I N E R , V I O L A S C H U LT Z E , B E R N D
R O S E N K R AN Z , S TE FAN H . E . K AU F M A N N TI M O
U L R I C H S , D E B O R AH N O V I C K I , F R AN C E S C O
N O R E L L I , M AR I O C O N TO R N I
G AS T R O E N TE R O L O G Y 2 0 0 8 ;1 3 5 :7 8 7 – 7 9 5
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
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
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
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.
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)
MATERIALS AND METHODS
 Subjects
- Exclusion criteria: H. pylori 감염 또는 치료의 Hx,
최근 4주내에 PPI, antibiotics, bismuth로 치료한 Hx
- Serologically negative for H. pylori at screening
- Underwent a urea breath test at screening
• 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
RESULTS
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
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.
Figure 3. Antigen-driven IFNproduction by PBMC at different time
Figure 4. Antigen-specific antibody Response
and antigen-driven IFN-production
CONCLUSION
 The intramuscular H. pylori vaccine demonstrated
satisfactory safety and immunogenicity, produced
antigen-specific T-cell memory, and, therefore,
warrants further clinical study