Unique immunogenicity of hepatitis B virus DNA vaccine presented by live-attenuated Salmonella typhimurium

A novel vaccine for hepatitis B virus (HBV) was designed by putting a naked DNA vaccine carrying hepatitis B surface antigen (HBsAg) into live-attenua ted Salmonella typhimurium. Mucosal immunization by the oral route in mice showed significantly stronger cytotoxic T lymphocyte (CTL) response than re combinant HBsAg vaccination (P < 0.01 at an effector:target ratio of 100:1) , while comparable to intramuscular naked DNA immunization at all effector: target ratios. Contrary to previous reports on naked DNA vaccines given int ramuscularly, the IgG antibody response induced by the mucosal DNA vaccine is relatively weak when compared to recombinant HBsAg vaccine (P < 0.001 at day 21). These findings are supported by a high interferon-gamma but a low interleukin-4 level detected in the supernatant of splenic cell cultures o btained from mucosally immunized mice. As distinct to recombinant HBsAg vac cine which is effective for protection, oral mucosal DNA vaccine should be considered as a candidate for therapeutic immunization in chronic HBV infec tion, donor immunization before adoptive transfer of HBV-specific CTL to HB sAg positive bone marrow transplant recipients, and immunization of non-res ponders to recombinant HBsAg vaccine. This strongly cellular and relatively absent humoral response may make this vaccine a better candidate as a ther apeutic vaccine for chronic HBV carriers than naked DNA vaccines, as the hu moral response is relatively less important for the clearance of HBV from h epatocytes, but its presence may lead to side effects such as serum sicknes s and immune complex deposition in chronic HBV carriers. (C) 2001 Elsevier Science Ltd. All rights reserved.