Recombinant varicella-zoster virus vaccines as platforms for expression of foreign antigens

Abstract

Varicella-zoster virus (VZV) vaccines induce immunity against childhood chickenpox and against shingles in older adults. The safety, efficacy, and widespread use of VZV vaccines suggest that they may also be effective as recombinant vaccines against other infectious diseases that affect the young and the elderly. The generation of recombinant VZV vaccines and their evaluation in animal models are reviewed. The potential advantages and limitations of recombinant VZV vaccines are addressed.

Figure 1

Cosmid approach to generate rVZV. (a) The 125 kb VZV genome consists of a unique long (UL) component flanked by internal and terminal inverted repeat sequences (IRL and TRL) covalently linked to a unique short (US) component bracketed by internal and terminal inverted repeats (IRS and TRS) [17]. (b) Four cosmids (30–45 kb), representing the entire VZV genome, are transfected into MeWo cells yields infectious virus. In this example, a foreign gene with a promoter is inserted into cosmid A, within the intergenic region between VZV ORFs 12 and 13.

Figure 2

VZV-BAC approach to generate rVZV. BAC sequences are inserted into the VZV genome within the intergenic region between ORFs 11 and 12 and maintained within E. coli. A foreign gene of interest (goi) with promoter is inserted between ORFs 65 and 66. rVZV-BAC DNA is transfected into MeWo cells to generate infectious rVZV. BAC sequences flanked by lox P sites (∗) may be removed from the VZV genome by Cre recombination.