Nucleic acid hepatitis B virus (HBV) vaccine: current status

Hepatitis B virus (HBV) infection is considered to be one of the diseases c ausing a serious public health problem throughout the world. In the South E ast, HBV infection remains the cause of morbidity and mortality in a signif icantly high number of cases of all age groups. Though a vaccine is already available to protect against this infection, the problems associated with dose schedule, number of doses, protection rendered, and response in differ ent populations of existing vaccine, indicate a need of further improvement in current HBV vaccine. This review discusses an advance made in the devel opment of a new generation of HBV vaccine with increased efficacy and bette r safety. Using the fact that non-replicating DNA plasmids encoding reporte r genes can be internalised and encoded proteins expressed by muscle cells following injection into them, HBsAg was chosen as a model for DNA-mediated immunisation in mice. This device produced major histocompatibility comple x (MHC)-restricted cytotoxic T-lymphocytes (CTL) and T-helper response agai nst HBsAg in them. The lymphocytes involved in CTL were found to be CD3 +, CD4 and CD8 +. T-helper response was predominantly and exclusively of Th1 t ype. Intramuscular injection of plasmid vectors containing HBV envelope pro teins induced antibodies to HBsAg particles having kinetic properties and s pecificity similar to those occurring during HBV infection in human beings. Both humoral response, as well as CTL, were found to depend on the amount and existence of the intramuscular reservoir of protein produced by muscle fibres. The titre of antibodies produced was recorded to be more than the p rotective level in the majority of cases. Like HBsAg, HBcAg vectors were al so demonstrated to be immunogenic, inducing high titres of antibodies in la rge animals. Thus, all these studies, though still at an early stage in the development of this new generation of HBV vaccine, clearly demonstrate the possibility of a new HBV vaccine capable of overcoming the problems associ ated with current vaccines. (C) 1998 Elsevier Science Ireland Ltd. All righ ts reserved.