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
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