Director, Head of Tolerance Research Therapy Area Nykode Therapeutics Oslo, Oslo, Norway
Abstract Text: Autoimmune diseases affect about 4% of the world population and hold great unmet medical need for the development of novel treatments.
Tolerogenic vaccination strategies aim to recalibrate disease-causing effector and protective regulatory responses in an antigen-specific manner that preserve protective immunity.
Nykode Therapeutics has developed a platform that targets antigens directly to antigen presenting cells (APCs) using a modular dimeric protein format known as a Vaccibody.
Here, Vaccibody vaccines were designed to deliver a tolerogenic response toward disease-associated antigens via specific APC-receptor-targeting. The Vaccibody vaccines were tested for their tolerogenic potential in the Experimental Autoimmune Encephalomyelitis (EAE) model and in Non-Obese Diabetic (NOD) mice either alone or combined with co-expression of immune-modulatory proteins in a multicistronic plasmid DNA.
In the EAE model, recombinant Vaccibody vaccines effectively treated EAE disease using targeting units toward two different receptors on APCs. The vaccine showed potent disease protection in preventive and early therapeutic settings associated with reduced antigen-specific pro-inflammatory cytokine release. The response was found to be dose-dependent, antigen-specific and APC-receptor-targeting dependent.
In NOD mice, vaccination with Vaccibody encoding plasmid DNA effectively delayed the development of spontaneous autoimmune diabetes; co-expression of selected immune-modulators resulted in full protection from diabetes development with a durable response also post treatment withdrawal.
These data demonstrate the flexibility of novel APC-receptor-targeting Vaccibody vaccines able to deliver potent tolerogenic responses in two different mouse models of autoimmune disease.
