Vaccination of mice with live recombinant Salmonella typhimurium aroA against H-pylori:: parameters associated with prophylactic and therapeutic vaccine efficacy

被引:22
作者
Koesling, J [1 ]
Lucas, B [1 ]
Develioglou, L [1 ]
Aebischer, T [1 ]
Meyer, TF [1 ]
机构
[1] Max Planck Inst Infect Biol, Dept Mol Biol, D-10117 Berlin, Germany
关键词
spleen colonization; gastric mucosa; humoral immune response;
D O I
10.1016/S0264-410X(01)00355-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Previously we described a recombinant attenuated Salmonella typhimurium aroA strain (SL3261 [pYZ97]) with constitutive expression of plasmid encoded Helicobacter pylori urease subunits A and B (UreAB). Single dose oral vaccination effectively induced prophylactic immunity against bacterial challenge in BALB/c mice. Here we successfully extended this approach to several mouse strains with allelic differences in NRAMP-1 and H-2 genes. The respective host determinants are known to influence the immune response against S. typhimurium. A comparative analysis of the vaccine efficacy in C57BL/6 and BALB/c mice showed that the live vaccine confers long lasting immunity in both strains (> 18 weeks). In C57BL/6 mice, protection was still observed 54 weeks while not all vaccinated BALB/c were immune when challenged after this time. BALB/c mice also needed higher doses of SL3261 [pYZ97] for full protection. We also demonstrate a therapeutic potential of SL3261 [pYZ97] in H. pylori infected BALB/c and C57BL/6 mice. Urease- and carrier- specific ser-um antibody responses as well as the level of colonization by the Salmonella were analyzed in both mouse strains after immunization with low (4 x 10(7) CFU) or high (I x 10(9) CFU) vaccine doses. The results are discussed in the context of inoculum size and the mode of antigen supply required for effective vaccination with recombinant Salmonella. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:413 / 420
页数:8
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