Vaccination of mice with live recombinant Salmonella typhimurium aroA against H. pylori: parameters associated with prophylactic and therapeutic vaccine efficacy.
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 serum 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 (1 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.
Koesling
J
J
Max Planck Institute for Infection Biology, Department of Molecular Biology, Schumannstr. 21/22, D-10117 Berlin, Germany.
Lucas
B
B
Develioglou
L
L
Aebischer
T
T
Meyer
T F
TF
D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D016480:Helicobacter pylori / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics*; D013045:Species Specificity; D014510:Urease / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
D001428:Bacterial Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014510:Urease