Expression of Hepatitis B Virus Surface Antigen Gene in Mammalian, Yeast, and Insect Cells

Abstract

Hepatitis B virus (HBV) infections cause serious liver disease and are a worldwide major public health problem. Vaccines against human HBV have been developed in three different countries using formalin-inactivated 22-nm hepatitis B virus surface antigen (HBsAg) particles from chronic active hepatitis patients. The hepatitis B virus vaccine has proved effective in terms of producing a protective level of circulating antibodies in the majority of persons vaccined. However, the vaccine supply is limited. The cost of vaccination is among the highest of all vaccines currently available. In order to overcome these problems, recombinant DNA techniques have been applied, and the viral genome has been cloned, sequenced, and expressed in various heterologous expression systems. Recently, a subunit vaccine was developed by expressing the cloned HBsAg gene in yeast. However, the cost of the vaccine has not yet been reduced significantly. A subunit vaccine developed by recombinant DNA technology must fulfill certain requirements, such as potency, purity, and lower cost of production. Thus, one of the most active areas of recombinant DNA technology in the past several years has been the search for an expression system that will produce large quantities of desired gene products, provide protein modification similar to that of the naturally occurring proteins, and allow for the secretion of the expressed proteins out of cells. This chapter compares the level of expression and antigenicity of HBsAg expressed in mammalian, yeast, and insect cell systems, using recombinant DNA vector.