The aim of this proposal is to investigate the use of the heat shock protein hsp70 as a potent adjuvant for the generation of immune responses against non- covalently bound antigenic peptides. They have devised a new method for the in vitro reconstitution of immunogenic hsp70:peptide complexes using hybrid peptides containing an hsp70 binding sequence. The resulting increased affinity of the peptide epitope for hsp70 allowed them to elicit strong immune responses against an epitope from ovalbumin and to show tumor regression in two model systems. Here they propose to reproduce these observations with a clinically relevant epitope from Herpes Simplex Virus (HSV). The following two specific aims will be addressed: 1) To test their hypothesis that immunization with the HSV epitope bound to hsp70 as a hybrid peptide will generate a potent cellular immune response as measured by performing a series of cytotoxic T lymphocyte killing assays, and 2) to establish that this immune response is potent enough to cause the regression of a model tumor which presents the HSV peptide at its cell surface. These experiments should illustrate the potential of this approach to serve as a platform technology for the development of vaccines against tumors and infectious agents.
Mojave intends to develop its platform technology using human hsp70 and hybrid peptide epitopes to generate vaccines against cancer and infectious diseases.
