Effective Antigen-Specific Immunotherapy in the Marmoset Model of Multiple Sclerosis

Abstract

Mature T cells initially respond to Ag by activation and expansion, but high and repeated doses of Ag cause programmed cell death and can suppress T cell-mediated diseases in rodents. We evaluated repeated systemic Ag administration in a marmoset model of experimental allergic encephalomyelitis that closely resembles the human disease multiple sclerosis. We found that treatment with MP4, a chimeric, recombinant polypeptide containing human myelin basic protein and human proteolipid protein epitopes, prevented clinical symptoms and did not exacerbate disease. CNS lesions were also reduced as assessed in vivo by magnetic resonance imaging. Thus, specific Ag-directed therapy can be effective and nontoxic in primates.

Metabolically inactive insulin analogue does not prevent autoimmune diabetes in NOD mice

“…Eliminating antigen-specific T cell clones by RICD is an exciting strategy for tolerance induction and can prevent or treat experimental autoimmune diseases [17, 18]. Parenteral insulin administration in individuals with risk of type 1 diabetes has not prevented disease, perhaps because the risk of hypoglycaemia limits the dose of insulin administered [4, 19, 20].…”

IFN-β Facilitates Neuroantigen-Dependent Induction of CD25+ FOXP3+ Regulatory T Cells That Suppress Experimental Autoimmune Encephalomyelitis

“…EAE has been successfully controlled by different strategies of tolerogenic vaccination (16–19), and several of these tolerogenic vaccine strategies have been advanced in MS as a means to specifically target pathogenic myelin-specific T cells. Tolerogenic vaccine approaches that emerged from studies of EAE into clinical testing in MS have been based on subcutaneous injection (20) or oral delivery (21) of various myelin basic protein preparations, direct administration of myelin basic protein peptide (MBP8298, Dirucotide) (22–24), or administration of a fusion protein comprised of myelin basic protein and proteolipid protein (PLP) epitopes (MP4) (25, 26). Although these approaches had success in EAE, attempts to translate these myelin-specific vaccine strategies in MS did not show robust clinical efficacy.…”

Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis

“…Because of ''determinant spreading,'' they may drift into new patterns over time (37,38). Several groups have designed chimeric proteins combining more than one myelin autoantigen for therapy (39,40). It will be difficult to cover the entirety of encephalitogenic proteins for therapy.…”