Myelin Peptide-Mannan Conjugate Multiple Sclerosis Vaccines: Conjugation Efficacy and Stability of Vaccine Ingredient.

George Deraos,Kostas Kelaidonis,Vasso Apostolopoulos,Emmanuel Topoglidis,John Matsoukas,Jack Feehan,Elizabeth Matsoukas,Andreas G. Tzakos,Md Kamal Hossain

doi:10.3390/vaccines9121456

Abstract

Myelin peptide–mannan conjugates have been shown to be potential vaccines in the immunotherapy of multiple sclerosis. The conjugates are comprised from the epitope peptide and the polysaccharide mannan which transfers as a carrier the antigenic peptide to dendritic cells that process and present antigenic peptides at their surface in complex with MHC class I or class II resulting in T-cell stimulation. The conjugation of antigenic peptide with mannan occurs through the linker (Lys–Gly)5, which connects the peptide with the oxidized mannose units of mannan. This study describes novel methods for the quantification of the vaccine ingredient peptide within the conjugate, a prerequisite for approval of clinical trials in the pursuit of multiple sclerosis therapeutics. Myelin peptides, such as MOG35–55, MBP83–99, and PLP131–145 in linear or cyclic form, as altered peptide ligands or conjugated to appropriate carriers, possess immunomodulatory properties in experimental models and are potential candidates for clinical trials.

Highlights

Multiple sclerosis (MS) is an inflammatory autoimmune-mediated disorder of the central nervous system involving a complex immune activation response, including T cells, B cells, and pro-inflammatory cytokines which attack the myelin sheath [1–7]
This work aimed to develop an analytical method for the quantification of mannan–peptide conjugates, which have shown to be good candidates for vaccines/immunotherapeutics against MS, and to investigate the role of (KG)5
Towards clinical evaluation in humans and obtaining approval for clinical trials of mannan–peptide conjugates, it is an important prerequisite to quantify the peptide within the conjugate or any potential degradants over time

Summary

Introduction

Multiple sclerosis (MS) is an inflammatory autoimmune-mediated disorder of the central nervous system involving a complex immune activation response, including T cells, B cells, and pro-inflammatory cytokines which attack the myelin sheath [1–7]. The immunodominant epitopes that are recognized by CD4+ Th1 cells are MBP83–99, PLP139–151, and MOG35–55 These epitopes have been used as tools in our and other studies that have led to the development of a series of mutated linear and cyclic peptide analogues, studied in animal models, and evaluated for immunomodulation in peripheral blood mononuclear cells from patients with MS [18–20]. These studies have shown that cyclic analogues are more stable to enzymatic proteolysis, bind well to major histocompatibility class II molecules, and antagonize Th1 cells, representing good candidates for their evaluation as immune modulators against MS [18]. A peptide on its own is not fully immunogenic and requires a carrier to deliver it to antigen-presenting cells

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