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

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.