LEAPS therapeutic vaccines as antigen specific suppressors of inflammation in infectious and autoimmune diseases.

Abstract

The L.E.A.P.S.(™) (Ligand Epitope Antigen Presentation System) technology platform has been used to develop immunoprotective and immunomodulating small peptide vaccines for infectious and autoimmune diseases. Several products are currently in various stages of development, at the pre-clinical stage (in animal challenge efficacy studies). Vaccine peptides can elicit protection of animals from lethal viral (herpes simplex virus [HSV-1] and influenza A) infection or can block the progression of autoimmune diseases (e.g. rheumatoid arthritis as in the collagen induced arthritis (CIA] or experimental autoimmune myocarditis (EAM) models). L.E.A.P.S. technology is a novel T-cell immunization technology that enables the design and synthesis of non-recombinant, proprietary peptide immunogens. Combination of a small peptide that activates the immune system with another small peptide from a disease-related protein, thus a conjugate containing both an Immune Cell Binding Ligand (ICBL) and a disease specific epitope, which allows the L.E.A.P.S. vaccines to activate precursors to differentiate and become more mature cells that can initiate and direct appropriate T cell responses. As such, readily synthesized, defined immunogens can be prepared to different diseases and are likely to elicit protection or therapy as applicable in humans as they are in mice. L.E.A.P.S. vaccines have promise for the treatment of rheumatoid arthritis and other inflammatory diseases and for infections, such as influenza and HSV1. The protective responses are characterized as Th1 immune and immunomodulatory responses with increased IL-12p70 and IFN-γ (Th1 cytokines) but reduced inflammatory cytokines TNF-α, IL-1 and IL-17 (Th2 and Th17 cytokines) and concomitant changes in antibody subtypes. LEAPS immunogens have been used directly in vivo or as ex vivo activators of DC which are then administered to the host.