IMMUNIZATION WITH A LYMPHOCYTIC CHORIOMENINGITIS VIRUS PEPTIDE MIXED WITH HEAT-SHOCK-PROTEIN-70 RESULTS IN PROTECTIVE ANTIVIRAL IMMUNITY AND SPECIFIC CYTOTOXIC T-LYMPHOCYTES

Heat shock proteins (hsp's) isolated from murine cancer cells can elic it protective immunity and specific cytotoxic T lymphocytes (CTLs) by channeling tumor-derived peptides bound to hsp's to the major histocom patibility class I antigen presentation pathway. Here we have investig ated if hsp70 can be used in a novel peptide vaccine for the induction of protective antiviral immunity and memory CTLs. A CTL epitope from the well-defined lymphocytic choriomeningitis virus (LCMV) system was mixed with recombinant hsp70 in vitro under conditions that optimize p eptide binding to hsp70. Mice were immunized with the hsp70-peptide mi xture and challenged with LCMV. Virus titers were reduced 10-100-fold in these mice compared to control mice. Immunization with the hsp70-pe ptide mixture resulted in the development of CTL memory cells that cou ld be reactivated during LCMV infection, and that in a Cr-51-release a ssay could lyse cells pulsed with the same peptide, but not cells puls ed with another LCMV peptide. These results show that hsp70 can be use d with CTL epitopes to induce efficient protective antiviral immunity and the generation of peptide-specific CTLs. The results also demonstr ate the usefulness of hsp70 as an alternative to adjuvants and DNA vec tors for the delivery of CTL epitopes to antigen-presenting cells.