Immunization with chaperone-peptide complex induces low-avidity cytotoxic T lymphocytes providing transient protection against herpes simplex virus infection

Heat shock proteins loaded with viral peptides were shown to induce a CD8() T cell response and confer protective immunity against challenge with her pes simplex virus (HSV). The delivery system consisted of recombinant human hsp70 coupled to the peptide SSIEFARL, which is the immunodominant peptide epitope, recognized by HSV specific T cells in C57BL/6 mice. Immunization resulted in CD8(+) T-cell responses, measured by peptide-specific tetramers and peptide-induced intracellular gamma interferon expression and cytotoxi city, similar to responses resulting from immunization with a recombinant v accinia virus that expressed SSIEFARL as a minigene (VvgB) and UV-inactivat ed HSV. However, the durability of the hsp70-SSIEFARL response was less tha n that resulting from VvgB and HSV immunization and in addition the CDS' T- cell responses in the memory phase were functionally less effective. Mice c hallenged soon after immunization showed excellent immunity, but by 90 days postimmunization this had waned to be significantly less than the level of immunity in both VvgB- and HSV-immunized mice.