Varicella-zoster virus as a live vector for the expression of foreign genes

Abstract

The previous demonstration of the efficacy and tolerability of the Oka strain of varicella-zoster virus (VZV) in clinical trials involving vaccination of both normal and immunocompromised individuals has laid the foundation for its use in preventing chickenpox. In this context, VZV could be useful as a vector for vaccinating against other infectious agents as well. As an initial application, a live recombinant VZV expressing Epstein-Barr virus (EBV) membrane glycoproteins (gp350/220) was generated by inserting a gene fusion of the VZV gpI promoter and hydrophobic leader-encoding sequence with the gp350/220 coding sequence into the thymidine kinase (TK) gene of VZV (Oka). Insertion of the foreign DNA into the thymidine kinase gene was demonstrated by Southern blot analysis and the ability of the recombinant virus to replicate in the presence of bromodeoxyuridine. RNA splicing, glycosylation, and plasma membrane presentation of gp350/220 in cells infected with the recombinant virus were similar to those seen in EBV-infected cells. In addition, the expression of VZV-specific glycoproteins was unaltered by the concomitant expression of this large foreign glycoprotein. Thus, VZV can be used as a live viral vector for active immunization against EBV and other pathogens.