Expression of hepatitis B virus surface antigen determinants in Lactococcus lactis for oral vaccination.

Lactococcus lactis with non-pathogenic and non-colonizing properties is an attractive candidate for delivering biologically active proteins by mucosal routes. In this report we described recombinant L. lactis applicable for the development of live mucosal vaccine against hepatitis B virus (HBV). The PreS region of the HBV surface antigen alone or combined with "a" determinant of S region (PreSa) was cloned and expressed in the food grade bacterium L. lactis using a nisin-controlled expression (NICE) system. Western blot analysis indicated that both PreS and PreSa fusion proteins were successfully expressed in L. lactis after nisin induction. Oral immunization of BALB/c mice with PreS and PreSa-producing strains induced both mucosal (intestinal IgA) and systemic (serum IgG) immune responses against HBV at the same magnitude. Two additional groups of mice given L. lactis expressing human interferon-alpha 2b as an adjuvant with the PreS or PreSa-producing strains produced higher IgG but not IgA antibody responses. These results indicated that the lactococci-derived vaccines could be promising candidates as alternative HBV vaccines for preventing hepatitis B.