Vaccination of mice with live recombinant Salmonella typhimurium aroA against H-pylori: parameters associated with prophylactic and therapeutic vaccine efficacy
J. Koesling et al., Vaccination of mice with live recombinant Salmonella typhimurium aroA against H-pylori: parameters associated with prophylactic and therapeutic vaccine efficacy, VACCINE, 20(3-4), 2001, pp. 413-420
Previously we described a recombinant attenuated Salmonella typhimurium aro
A strain (SL3261 [pYZ97]) with constitutive expression of plasmid encoded H
elicobacter pylori urease subunits A and B (UreAB). Single dose oral vaccin
ation effectively induced prophylactic immunity against bacterial challenge
in BALB/c mice. Here we successfully extended this approach to several mou
se strains with allelic differences in NRAMP-1 and H-2 genes. The respectiv
e host determinants are known to influence the immune response against S. t
yphimurium. A comparative analysis of the vaccine efficacy in C57BL/6 and B
ALB/c mice showed that the live vaccine confers long lasting immunity in bo
th strains (> 18 weeks). In C57BL/6 mice, protection was still observed 54
weeks while not all vaccinated BALB/c were immune when challenged after thi
s time. BALB/c mice also needed higher doses of SL3261 [pYZ97] for full pro
tection. We also demonstrate a therapeutic potential of SL3261 [pYZ97] in H
. pylori infected BALB/c and C57BL/6 mice. Urease- and carrier- specific se
r-um antibody responses as well as the level of colonization by the Salmone
lla 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 i
n the context of inoculum size and the mode of antigen supply required for
effective vaccination with recombinant Salmonella. (C) 2001 Elsevier Scienc
e Ltd. All rights reserved.