Immunization with attenuated Salmonella typhimurium producing catalase in protection against gastric Helicobacter pylori infection in mice

被引:26
作者
Chen, MH
Chen, J
Liao, WJ
Zhu, SL
Yu, J
Leung, WK
Hu, PJ
Sung, JJY
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastroenterol, Guangzhou 510080, Peoples R China
[2] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China
关键词
Helicobacter pylori; vaccine; catalase; Salmonella typhimurium;
D O I
10.1111/j.1523-5378.2003.00182.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Aim. To evaluate the protective effect of live attenuated Salmonella typhimurium expressing catalase against gastric Helicobacter pylori infection in mice, and to explore the underlying mechanisms of the protective immune reaction. Materials and Methods. The H. pylori catalase gene was introduced into attenuated S. typhimurium strain SL3261. C57BL/6 mice were orally immunized with the SL3261 vaccine strain expressing catalase or with SL3261 alone or phosphate-buffered saline (PBS). Mice were sacrificed 4 weeks after immunization and 5 weeks after H. pylori challenge, respectively. Results. All PBS control mice were infected. Eight of 13 (61.5%) mice immunized with the SL3261 vaccine strain and three of 14 (21%) mice immunized with SL3261 alone showed protection against H. pylori infection. Serum anti-H. pylori IgG2a levels of S. typhimurium-immunized mice were higher than those of PBS controls, both before and after H. pylori challenge, while there were no differences for IgG1 and IgA. Similarly, mRNA expression of interleukin (IL)-2, IL-12 and interferon-gamma in the gastric mucosa of S. typhimurium-immunized mice was significantly higher than that of PBS controls both before and after challenge. Moreover, S. typhimurium-immunized mice were characterized by marked infiltration of lymphocyte and mononuclear cells in the gastric mucosa after challenge. IL-4 and IL-10 were not detected in any of the three groups. IL-6 expression was increased in the PBS group compared with the S. typhimurium-immunized groups after challenge. Conclusions. This study demonstrates that oral immunization of mice with catalase delivered by an attenuated S. typhimurium strain offers protection against H. pylori infection. This protective immunity was mediated through a predominantly Th1-type response and was associated with post-immunization gastritis.
引用
收藏
页码:613 / 625
页数:13
相关论文
共 48 条
[11]  
Dubois A, 1998, INFECT IMMUN, V66, P4340
[12]   Helicobacter pylori [J].
Dunn, BE ;
Cohen, H ;
Blaser, MJ .
CLINICAL MICROBIOLOGY REVIEWS, 1997, 10 (04) :720-+
[13]   Murine splenocytes induce severe gastritis and delayed-type hypersensitivity and suppress bacterial colonization in Helicobacter pylori-infected SCID mice [J].
Eaton, KA ;
Ringler, SR ;
Danon, SJ .
INFECTION AND IMMUNITY, 1999, 67 (09) :4594-4602
[14]   Gastritis in urease-immunized mice after Helicobacter felis challenge may be due to residual bacteria [J].
Ermak, TH ;
Ding, R ;
Ekstein, B ;
Hill, J ;
Myers, GA ;
Lee, CK ;
Pappo, J ;
Kleanthous, HK ;
Monath, TP .
GASTROENTEROLOGY, 1997, 113 (04) :1118-1128
[15]  
FERRERO RL, 1995, GUT S1, V37, pA203
[16]   A murine model of intranasal immunization to assess the immunogenicity of attenuated Salmonella typhi live vector vaccines in stimulating serum antibody responses to expressed foreign antigens [J].
Galen, JE ;
GomezDuarte, OG ;
Losonsky, GA ;
Halpern, JL ;
Lauderbaugh, CS ;
Kaintuck, S ;
Reymann, MK ;
Levine, MM .
VACCINE, 1997, 15 (6-7) :700-708
[17]   Antimicrobial resistance and Helicobacter pylori [J].
Goddard, AF ;
Logan, RPH .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1996, 37 (04) :639-643
[18]   The attenuated Salmonella vaccine approach for the control of Helicobacter pylori-related diseases [J].
Gómez-Duarte, OG ;
Bumann, D ;
Meyer, TF .
VACCINE, 1999, 17 (13-14) :1667-1673
[19]   Protection of mice against gastric colonization by Helicobacter pylori by single oral dose immunization with attenuated Salmonella typhimurium producing urease subunits A and B [J].
Gómez-Duarte, OG ;
Lucas, B ;
Yan, ZX ;
Panthel, K ;
Haas, R ;
Meyer, TF .
VACCINE, 1998, 16 (05) :460-471
[20]   Local secretory immunoglobulin A and postimmunization gastritis correlate with protection against Helicobacter pylori infection after oral vaccination of mice [J].
Goto, T ;
Nishizono, A ;
Fujioka, T ;
Ikewaki, J ;
Mifune, K ;
Nasu, M .
INFECTION AND IMMUNITY, 1999, 67 (05) :2531-2539