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

被引:14
作者
Sanchez, V
Gimenez, S
Haensler, J
Geoffroy, C
Rokbi, B
Seguin, D
Lissolo, L
Harris, B
Rizvi, F
Kleanthous, H
Monath, T
Cadoz, M
Guy, B
机构
[1] Aventis Pasteur, Dept Res, F-69280 Marcy Letoile, France
[2] Acambis, Cambridge, MA 02139 USA
来源
FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY | 2001年 / 30卷 / 02期
关键词
D O I
10.1016/S0928-8244(00)00243-1
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. <(c)> 2001 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.
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页码:157 / 165
页数:9
相关论文
共 45 条
[1]  
AKHIANI A, 1998, EUR M H PYL IMM PATH
[2]   Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori [J].
Alm, RA ;
Ling, LSL ;
Moir, DT ;
King, BL ;
Brown, ED ;
Doig, PC ;
Smith, DR ;
Noonan, B ;
Guild, BC ;
deJonge, BL ;
Carmel, G ;
Tummino, PJ ;
Caruso, A ;
Uria-Nickelsen, M ;
Mills, DM ;
Ives, C ;
Gibson, R ;
Merberg, D ;
Mills, SD ;
Jiang, Q ;
Taylor, DE ;
Vovis, GF ;
Trost, TJ .
NATURE, 1999, 397 (6715) :176-180
[3]   Changes in Helicobacter pylori ultrastructure and antigens during conversion from the bacillary to the coccoid form [J].
Benaissa, M ;
Babin, P ;
Quellard, N ;
Pezennec, L ;
Cenatiempo, Y ;
Fauchere, JL .
INFECTION AND IMMUNITY, 1996, 64 (06) :2331-2335
[4]  
Blanchard TG, 1999, CURR TOP MICROBIOL, V241, P181
[5]   Cationic lipid DC-Chol induces an improved and balanced immunity able to overcome the unresponsiveness to the hepatitis B vaccine [J].
Brunel, F ;
Darbouret, A ;
Ronco, J .
VACCINE, 1999, 17 (17) :2192-2203
[6]   IMMUNIZATION AGAINST GASTRIC HELICOBACTER INFECTION IN A MOUSE HELICOBACTER-FELIS MODEL [J].
CHEN, MH ;
LEE, A ;
HAZELL, S .
LANCET, 1992, 339 (8801) :1120-1121
[7]   Coccoid and spiral Helicobacter pylori differ in their abilities to adhere to gastric epithelial cells and induce interleukin-8 secretion [J].
Cole, SP ;
Cirillo, D ;
Kagnoff, MF ;
Guiney, DG ;
Eckmann, L .
INFECTION AND IMMUNITY, 1997, 65 (02) :843-846
[8]  
CORREA P, 1995, AM J SURG PATHOL, V19, pS37
[9]  
Corthésy-Theulaz IE, 1998, INFECT IMMUN, V66, P581
[10]   PROTECTION OF GERM-FREE MICE FROM INFECTION BY HELICOBACTER-FELIS AFTER ACTIVE ORAL OR PASSIVE IGA IMMUNIZATION [J].
CZINN, SJ ;
CAI, A ;
NEDRUD, JG .
VACCINE, 1993, 11 (06) :637-642