Safety and immunogenicity of an intramuscular Helicobacter pylori vaccine in noninfected volunteers: a phase I study.
BACKGROUND
Helicobacter pylori infection is among the most common human infections and the major risk factor for peptic disease and gastric cancer. Immunization with vaccines containing the H pylori vacuolating cytotoxin A (VacA), cytotoxin-associated antigen (CagA), and neutrophil-activating protein (NAP), alone or in combination, have been shown to prevent experimental infection in animals.


OBJECTIVE
We sought to study the safety and immunogenicity of a vaccine consisting of recombinant VacA, CagA, and NAP given intramuscularly with aluminium hydroxide as an adjuvant to noninfected healthy subjects.


METHODS
This controlled, single-blind Phase I study randomized 57 H pylori-negative volunteers into 7 study arms exploring 2 dosages (10 and 25 microg) of each antigen and 3 schedules (0, 1, 2 weeks; 0, 1, 2 months; and 0, 1, 4 months) versus alum controls. All participants were followed for 5 months. Thirty-six subjects received a booster vaccination 18-24 months after the completion of the primary vaccination.


RESULTS
Local and systemic adverse reactions were mild and similar in placebo and vaccine recipients on the monthly schedules. All subjects responded to 1 or 2 of the antigens and 86% of all vaccines mounted immunoglobulin G antibody responses to all 3 antigens. Vaccinees exhibited an antigen-specific cellular response. Vaccination 18-24 months later elicited anamnestic antibody and cellular responses.


CONCLUSIONS
This intramuscular H pylori vaccine demonstrated satisfactory safety and immunogenicity, produced antigen-specific T-cell memory, and, therefore, warrants further clinical study.
Malfertheiner
Peter
P
Otto-von-Guericke Universitaet, Department of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, Germany.
Schultze
Viola
V
Rosenkranz
Bernd
B
Kaufmann
Stefan H E
SH
Ulrichs
Timo
T
Novicki
Deborah
D
Norelli
Francesco
F
Contorni
Mario
M
Peppoloni
Samuele
S
Berti
Duccio
D
Tornese
Daniela
D
Ganju
Jitendra
J
Palla
Emanuela
E
Rappuoli
Rino
R
Scharschmidt
Bruce F
BF
Del Giudice
Giuseppe
G
D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide; D000907:Antibodies, Bacterial / Q000097:blood; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D016037:Single-Blind Method; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; C092412:neutrophil-activating protein A, Helicobacter pylori; D015847:Interleukin-4; D000536:Aluminum Hydroxide; D007371:Interferon-gamma