INDUCTION OF PRIMARY, ANTIVIRAL CYTOTOXIC, AND PROLIFERATIVE RESPONSES WITH ANTIGENS ADMINISTERED VIA DENDRITIC CELLS

Cytotoxic T lymphocytes (CTL) play an essential role in recovery from viral infections, but induction of CTL responses with nonreplicating a ntigens is difficult to achieve. Exogenous antigens, such as viral pro teins and peptides, normally induce CD4+ T-cell responses unless appro priately delivered to the major histocompatibility complex class I ant igen presentation pathway. In vitro studies performed to address this issue revealed a similar scenario, and primary CTL induction with nonr eplicating antigens has rarely been reported. This study demonstrated primary antiviral CTL induction in vitro with exogenous antigens deliv ered in vivo to dendritic cells. This study also evaluated the efficac y of glycoprotein B peptide (free or encapsulated in liposomes), pepti de-tripalmitoyl-S-glyceryl cysteinyl conjugate (acylpeptide), and glyc oprotein B protein encapsulated in pH-sensitive liposomes as antigen d elivery vehicles. Our results show that higher levels of cytotoxicity against herpes simplex virus type 1 resulted from exposure of dendriti c cells to peptide-tripalmitoyl-S-glyceryl cysteinyl in liposomes. Mac rophages treated in a similar manner were not effective stimulators fo r primary CTL induction. Our data have relevance to the understanding of mechanisms of antigen processing and presentation and the design of antiviral vaccines.