DNA-mediated immunization to the hepatitis B surface antigen in mice: aspects of the humoral response mimic hepatitis B viral infection in humans.

Abstract

Intramuscular injection of plasmid DNA expression vectors encoding the three envelope proteins of the hepatitis B virus (HBV) induced humoral responses in C57BL/6 mice specific to several antigenic determinants of the viral envelope. The first antibodies appeared within 1-2 weeks after injection of DNA and included antibodies of the IgM isotype. Over the next few weeks, an IgM to IgG class switch occurred, indicating helper T-lymphocyte activity.Peak IgG titers were reached by 4-8 weeks after a single DNA injection and were maintained for at least 6 months without further DNA injections. The antibodies to the envelope proteins reacted with group-and subtype-specific antigenic determinants of the HBV surface antigen (HBsAg). Expression vectors encoding the major (S) and middle (preS2 plus S) envelope proteins induced antibodies specific to the S protein and the preS2 domain, and preS2 antibodies were prominent at early time points. In general, the expression vectors induced humoral responses in mice that mimic those observed in humans during the course of natural HBV infection.

Enhancement of immune responses to an HBV DNA vaccine by electroporation

“…The pCMV-M plasmid DNA [4] containing the gene for the medium form of HBV surface antigen (HBsAg) was obtained from Aldevron (Fargo, ND). The pVax-HBVc plasmid was made at Ichor by inserting the gene coding for the HBV core antigen (HBcAg) (synthesized by Retrogen, San Diego, CA) into the pVax backbone (Invivogen, Carlsbad, CA).…”

Designing gene therapy vectors: avoiding immune responses by using tissue-specific promoters

“…We have evaluated this possibility using a modification of our well-established DNA vaccine model whereby expression of HBsAg under the control of a ubiquitously expressed promoter induces strong antibodies against HBsAg (antiHBs) and cytotoxic T lymphocytes (CTL) responses. [12][13][14][15][16] Herein we show that expression of the same highly antigenic HBsAg protein does not elicit, or even prime, any immune responses when expressed under the control of muscle-specific creatine kinase (MCK) promoters that express poorly or not at all in cells of the lymphocytic lineage.…”

Multiepitopic HLA-A*0201-Restricted Immune Response Against Hepatitis B Surface Antigen After DNA-Based Immunization

“…The in vivo production of the Ag leads to a complete immune response, with production of Abs and the initiation of long-lasting CD4 ϩ -and CD8 ϩ -specific T cell responses (12). We have developed DNA immunization against HBV based on injection of vectors encoding hepatitis B surface Ag (HBsAg) (13,14). To date, several constructs have been tested in different animal models (mice and nonhuman primates) in which Abs (15,16), CD4 ϩ T cell proliferative responses (17), and CD8 ϩ CTL were induced (18 -20).…”