The use of DNA for the development of novel prophylactic and therapeutic vaccines against the hepatitis B virus.

Abstract

The prevention and control of new and existing hepatitis B virus (HBV) infections remains an important global health concern. Despite current global immunization efforts, new HBV infection continues to occur. It is estimated that about 350 million people worldwide are currently afflicted by viral persistence. This body of work explores the possibility of developing improved prophylactic and possibly therapeutic vaccines against HBV using DNA technology. It has become well established that the effective control of HBV infection requires the development of strong humoral and cell mediated immunity (CMI) including the production of the pro-inflammatory cytokines interferon (IFN) gamma and tumor necrosis factor (TNF) alpha that are associated with a CMI response. In the absence of these responses infection is not resolved and persistence ensues. The ability of DNA (either in the form of a DNA vaccine or as immunostimulatory DNA sequences in combination with protein antigens) to stimulate both humoral and cellular immune responses that include the production of IFNgamma and TNFalpha, makes them attractive candidates for development of novel prophylactic and therapeutic agents in the struggle against HBV infection. This work demonstrates that immunization strategies that include DNA technology were capable of controlling HBV gene expression in a hepatitis B surface antigen transgenic mouse model as well as provide protection against infectious HBV challenge in chimpanzees. The quality of the immune responses induced in the chimpanzees suggests that the therapeutic potential of these immunization strategies observed in the mouse model may also extend to higher primates.