Infectivity of herpes simplex virus type-1 (HSV-1) amplicon vectors in dendritic cells is determined by the helper virus strain used for packaging

Abstract

Herpes simplex virus type-1 (HSV-1) amplicon vectors are being explored for a wide range of potential applications, including vaccine delivery and immunotherapy of cancer. While extensive effort has been directed towards the improvement of the amplicon "payload" in these vectors, relatively little attention has been paid to the effect of the packaging HSV-1 strains on the biological properties of co-packaged amplicon vectors. We therefore compared the biological properties of amplicon stocks prepared using a panel of primary HSV-1 isolates, a molecularly cloned strain used to package helper-free amplicons (designated here as F5), and two laboratory isolates (KOS and strain 17, which is the parent of the F5 clone). This analysis revealed considerable inter-strain variability in the ability of amplicon stocks packaged by different primary HSV-1 isolates to efficiently transduce established cell lines and primary human dendritic cells (DC). Amplicons packaged by both the F5 molecularly cloned virus and its laboratory-adapted parent (strain 17) were very inefficient at transducing DC, when compared to amplicons packaged by KOS or by several of the primary virus isolates. These finding have important implications for the future development of improved amplicon-based vaccine delivery systems and suggest that DC tropism may be an instrinsic property of some HSV-1 strains, independent of passage history or molecular cloning.

Effects of Herpes Simplex Virus Amplicon Transduction on Murine Dendritic Cells

“…Minor changes in either HSV amplicon preparation or transduction protocol will greatly affect the efficiency of DC transduction and thus the outcome of immune responses. This is supported by results published by our collaborators Santos and colleagues, showing that transduction efficiencies of HSV amplicon stocks could be modulated by the particular strain of origin for helper virus used for HSV amplicon packaging (Santos et al, 2007).…”