The L.E.A.P.S. approach to vaccine development

Abstract

The Ligand Epitope Antigen Presentation System (L.E.A.P.S.) approach to vaccine development utilizes immune peptides to promote the immunogenicity and influence the type of immune response generated towards epitopes in peptides which may be too small to elicit an immune response. The covalent attachment of these immune peptides to the antigenic peptide promotes the interaction of the epitope with T cells (T cell binding ligand (TCBL)) or antigen presenting cells (immune cell binding ligand (ICBL)) and ultimately promotes binding with the T cell receptor on CD4 or CD8 T cells. The, J, ICBL/TCBL peptide derived from the beta-2-microglobulin chain of MHC I molecules promotes Th1 type responses to the antigenic peptide while the, G, ICBL/TCBL peptide derived from the beta chain of MHC II molecules promotes Th2 types of responses. The efficacy of this approach has been demonstrated by characterization of the immune responses to L.E.A.P.S. vaccines and by elicitation of protection from infectious challenge with herpes simplex virus and other pathogens. The protection studies show that the L.E.A.P.S. approach allows customization of the immune response appropriate for inducing protection from disease. The theory, background, examples and studies of the mechanism of action of the L.E.A.P.S. vaccines will be discussed.

CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model

“…The lack of antibody response to the J-ICBL is in agreement with previous studies [30][31][32][33][34]38,40]. Neither the sera from untreated CIA diseased mice nor the CIA plus etanercept sera had antibodies to the CEL-2000 vaccine components.…”

“…After incubation and washing as before, plates were reacted with OPD substrate and chromagen, and absorbance measured at 492 nm on a BioTek plate reader (Model EL808). In other assays the isotype of the reacting antibodies was determined using isotype-specific antibodies [29][30][31][32][33][34][35][36][37][38][39][40]. …”

A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine

“…Thus, four types of vaccines have been most carefully considered: 1. HSV-2 subunit vaccines [5], [6], [7], [8], [9], [10]; 2. gene-delivery vehicles that express HSV-2 proteins [11], [12], [13], [14], [15], [16], [17], [18], [19]; 3. replication-defective HSV-2 viruses [20], [21], [22], [23], [24], [25]; and 4. HSV-2 viruses that are overattenuated and/or unable to replicate in neurons [26], [27], [28], [29], [30], [31].…”

Maturation of dendritic cell precursors into IL12-producing DCs by J-LEAPS immunogens

“…The ligand antigen epitope presentation system (LEAPS) converts small peptides into immunogens by chemical conjugation to an immune cell binding ligand (ICBL) such as J ((DLLKNGERIEKVE), amino acid 38-50 from the beta-2-microglobulin) [11]. The JgD [12] and JH [13] heteroconjugate peptide immunogens consist of a peptide from the N-terminus of HSV-1 glycoprotein D (SLKMADPNRFRGKDLP, amino acid 8-23) or the HGP-30 (H) peptide from the pl7 HIV gag protein (YSVHQRIDVKDTKEALEKIEEEQNKSKKKA (aa 85-115)) conjugated to the J-ICBL through a triglycine linker.…”