1105 HOW VARICELLA VACCINE WORKS: AN APPRAISAL WITH MONOCLONAL ANTIBODIES

Abstract

Studies with the live attenuated strain (VZV-Oka) of varicella zoster virus vaccine demonstrate a high degree of efficacy in protecting children with leukemia from contracting wild-type chickenpox. The purpose of this study was to determine which were the most important immunogenic proteins of VZV-Oka and to identify neutralization epitopic sites. Prior investigations of the immune response to wild type chickenpox indicate that the predominant antibody response is directed against the major viral glycoproteins. In order to evaluate VZV-Oka, murine monoclonal antibodies were produced against its viral glycoproteins. Specificities of antibodies were determined by techniques of immunoprecipitation and immunoblotting. By these studies we divided the glycoproteins into three groups: (1) gp118 (2) gp98/gp62/gp45 and (3) gp140/gp66. Biologic activity of each antibody was assayed by the technique of plaque reduction. A panel of antibodies against VZV gp118 were shown to possess marked neutralization activity (with titers to 1:40,000) against homologous and heterologous VZV strains. A titer of this magnitude indicates that glycoprotein gp118 of VZV-Oka harbors a major neutralization epitope. Glycoproteins gp140/gp66 also contained a complement-independent neutralization epitope but none was detected on the gp98 complex. These analyses with monoclonal antibodies define biologically important antigenic sites of VZV-Oka and suggest a role for the same glycoproteins in any future subunit vaccine.