Formulations of single or multiple H. pylori antigens with DC Chol adjuvant induce protection by the systemic route in mice. Optimal prophylactic combinations are different from therapeutic ones.
The ability to induce a protective response against Helicobacter pylori infection has been investigated by systemic immunization of mice with urease formulated with the cationic lipid DC Chol. This compound acts both as a formulating agent and as an adjuvant and induces a balanced Th1/Th2 response shown to be more effective for protection in our previous studies. Urease-DC Chol induced a significant protection in prophylaxis but not in therapeutic immunization. The protection level was between 1.5 and 2 log reduction of bacterial density measured by quantitative culture compared to unimmunized-infected mice. In parallel, the protective efficacy of other H. pylori antigens formulated in a similar way and administered with DC Chol was tested. These antigens were tested alone or in combination in prophylactic and therapeutic regimens. Some combinations of antigens induced a better prophylactic or therapeutic activity than urease alone (0.5-1.5 log further reduction in prophylaxis and therapy respectively, P<0.05). The combinations that induced the best protection were different in prophylaxis and therapy. In conclusion, DC Chol provides a convenient and efficient method to formulate different antigens even when they are present in non-compatible buffers initially. Moreover, the results obtained in protection against H. pylori with such formulations should lead the way to future clinical trials.
Sanchez
V
V
Aventis Pasteur, Campus Mérieux, Research Department, Marcy l'Etoile, France.
Gimenez
S
S
Haensler
J
J
Geoffroy
C
C
Rokbi
B
B
Seguin
D
D
Lissolo
L
L
Harris
B
B
Rizvi
F
F
Kleanthous
H
H
Monath
T
T
Cadoz
M
M
Guy
B
B
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015153:Blotting, Western; D002784:Cholesterol / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D007114:Immunization; D007167:Immunotherapy; D051379:Mice; D014510:Urease / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D002784:Cholesterol; D014510:Urease