Ligand epitope antigen presentation system vaccines against herpes simplex virus

Abstract

The Ligand Epitope Antigen Presentation System (L.E.A.P.S.) approach to vaccine development allowed construction of immunogens from defined T cell epitopes from herpes simplex virus (HSV) proteins that conferred protection against lethal challenge by the virus. This technology utilizes specific peptides which bind to CD4, CD8 or other proteins on the surface of T cells (T cell binding ligand (TCBL)), macrophage and dendritic cells (immune cell binding ligand (ICBL)) to promote the immunogenicity of an epitope, activate T cell and other protective responses, and direct the immune response to either a Th1 or a Th2 type of response. The J TCBL/ICBL is a peptide from beta-2-microglobulin which binds to the CD8 protein and promotes Th1 responses and the G TCBL/ICBL is a peptide from the beta chain of MHC II molecules that binds to the CD4 protein and promotes Th2 responses. Epitopes from the ICP27 (H1, H2), glycoprotein B (gB) and glycoprotein D (gD) proteins of HSV-1 were attached to either the J TCBL/ICBL or the G TCBL/ICBL. The JH1, JH2, JgB and JgD vaccines elicited DTH responses without antibody but conferred protection upon lethal challenge. Th1 related antibody was produced after challenge of the JgB and JgD immunized mice. Immunization with the GH1, GgB or GgD vaccines did not yield protection. The GgB and GgD produced Th2 related antibodies upon virus challenge. Initiation of the immune response by the JgD vaccine was dependent on functional CD4, CD8 expressing cells and interferon gamma and delivery of protection was dependent upon CD4 and interferon gamma. The L.E.A.P.S. HSV vaccines appear to elicit the appropriate immune responses for protection and further work is being performed to develop the JgD vaccine for human use.