INDUCTION OF SINGLE AND DUAL CYTOTOXIC T-LYMPHOCYTE RESPONSES TO VIRAL-PROTEINS IN MICE USING RECOMBINANT HYBRID TY-VIRUS-LIKE PARTICLES

The induction of cytotoxic T-lymphocyte (CTL) responses to viral prote ins is thought to be an essential component of protective immunity aga inst viral infections. Methods for generating such responses in a repr oducible manner would be of great value in vaccine development. We dem onstrate here that the recombinant antigen-presentation system based o n the yeast transposon (Ty) particle-forming pi protein is a potent me ans of inducing CTL responses to a variety of viral CTL epitopes, incl uding influenza virus nucleoprotein (two epitopes), Sendai virus and v esicular stomatitis virus nucleoproteins, and the V3 loop of human imm unodeficiency virus type-1 (HIV-I) gp120. CTL were primed by hybrid Ty -virus-like particles (VLP) carrying the minimal epitope or as much as 19 000 MW of protein. Ty-VLP carrying two different epitopes (dual-ep itope Ty-VLP) were capable of priming CTL responses in two different s trains of mice or against two epitopes in the same individual. Further more, co-administration of a mixture of two different Ty-VLP carrying single epitopes could induce responses to both epitopes in the same in dividual. Ty-VLP appear to represent a reproducible and flexible syste m for inducing CTL responses in mice, and warrant further evaluation i n primates.