Immunological properties of recombinant HBsAg produced in yeast

Although currently available plasma-derived vaccines (PDV) against hepatitis B based on the surface antigen of the virus (HBsAg) are well-tolerated and effective, their supply is limited and time-consuming controls are necessary to assess their safety. It is therefore desirable that an alternative source of HBsAg be found. Recombinant DNA technology has provided the possibility of obtaining HBsAg in large quantities. However, it is important that a recombinant DNA hepatitis B vaccine be not only antigenically similar but also elicits a similar immune response in humans. Using the Ausria kit, the recombinant DNA vaccine of SmithKline Biologicals produced in yeast appears to have a higher antigenic content than a reference plasma-derived HBsAg preparation of similar purity when compared at equivalent protein concentrations. In competition experiments, however, antibodies obtained by immunization with PDV similarly recognized yeast-derived and plasma-derived antigens. Monoclonal antibodies directed to the common a determinant of the whole virus were also used to identify distinct epitopes on the recombinant DNA vaccine. The yeast-derived HBsAg is therefore antigenically similar to plasma-derived HBsAg. The yeast-derived vaccine (YDV) was highly immunogenic in mice, rabbits, goats, monkeys, chimpanzees, and humans. High titres of anti-HBs were reached in humans after three doses administered at 0, 1, and 6 months. The antibodies raised in humans after three doses of YDV were predominantly directed to the common a determinant. Competition studies using monoclonal antibodies raised against the whole virus showed that the antibodies had the same specificity as the antibodies induced by PDV. The affinity for the plasma-derived antigen of antibodies stimulated by YDV and PDV and antibodies present in the sera of convalescent subjects were also similar. Finally, competition experiments showed that the antibodies induced in humans by YDV and antibodies from convalescent subjects were directed to the same binding sites of the plasma-derived antigen. These studies indicate that the yeast-derived vaccine is immunologically similar to the plasma-derived vaccines both in vitro and in vivo and can therefore be expected to have similar protective efficacy.