Expression of Helicobacter pylori urease subunit B gene in Lactococcus lactis MG1363 and its use as a vaccine delivery system against H-pylori infection in mice

The use of Lactococcus lactis as an antigen delivery vehicle for mucosal im munisation has been proposed. To determine whether L. lactis could effectiv ely deliver Helicobacter pylori antigens to the immune system, a recombinan t L. lactis expressing H. pylori urease subunit B (UreB) was constructed. C onstitutive expression of UreB by a pTREX1 vector resulted in the intracell ular accumulation of UreB to approximate to 6.25% of soluble cellular prote in. Five different oral regimens were used to vaccinate C57BL/6 mice and th e immune response measured. One regimen, which consisted of four weekly dos es of 10(10) bacteria, followed after an interval of approximate to4 weeks by three successive daily doses, was able to elicit a systemic antibody res ponse to UreB in the mice, although subsequently, a similar regimen produce d a significant antibody response in only one out of six mice. The other th ree regimes, in which mice were vaccinated with two or three sets of three consecutive daily doses of recombinant bacteria over 30 days, failed to eli cit significant anti-UreB serum antibody responses. In three regimens, the immunised mice were then challenged by H. pylori strain SS1 and no protecti ve effect was observed. These findings suggest that any adjuvant effects of L. lactis are unlikely to be sufficient to produce an effective immune res ponse and to protect against H. pylori challenge, when used to deliver a we ak immunogen, such as UreB. (C) 2001 Elsevier Science Ltd. All rights reser ved.