THE SYNTHESIS AND IMMUNOGENICITY OF VARICELLA-ZOSTER VIRUS GLYCOPROTEIN-E AND IMMEDIATE-EARLY PROTEIN (IE62) EXPRESSED IN RECOMBINANT HERPES-SIMPLEX VIRUS-1

In order to evaluate the conditions for optimal expression and immunog enicity of varicella-zoster virus (VZV) proteins in a herpes simplex v irus-1 (HSV-1) vector, we selected the VZV glycoprotein E (gE), encode d by ORF 68 and the VZV product of ORF 62, an immediate-early major te gument protein (IE62). Three HSV/VZV recombinants were generated: (1) VZV gE protein coding sequences along with the promoter region were in serted,into the thymidine kinase (TK) gene of HSV-1 strain KOS; (2) VZ V gE expressed from the HSV-1 ICP4 promoter was inserted into the glyc oprotein C (gC) gene of HSV-1 strain F; and (3) VZV IE62 protein codin g sequences under the control of the HSV-1 ICP4 promoter were inserted into the gC gene of HSV-1 strain F. Immunoblot analysis and immunoper oxidase staining of infected cell monolayers demonstrated vector expre ssion of VZV proteins. Following intracranial inoculation in mice, bot h VZV gE-HSV (TK) and VZV IE62-HSV (gC) induced an IgG response agains t VZV gE or VZV IE62. When tested in cytotoxicity assays using T-lymph ocytes from VZV immune human donors, the range of precursor frequencie s for T-lymphocytes that recognized VZV gE or VZV IE62 was similar whe ther these proteins were expressed by HSV-1 or a vaccinia vector. Thes e experiments demonstrate that HSV-1 is a competent vector for express ion of these VZV proteins and support the feasibility of engineering a combined vaccine for these closely related alpha-herpesviruses. (C) 1 997 Elsevier Science B.V.