Utveckla tolerogena vacciner för reumatoid artrit: en ny metod för immunmodulering och sjukdomshantering.

Laura Romero-Castillo, Karolinska Institutet, 100000

Bakgrund och motivering

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, characterized by peripheral joint inflammation and bone destruction. The current medical treatments for established RA are nonspecific and expect major side effects. Therefore, there is a need for the development of more specific, safer and more effective therapeutic interventions. We propose a tolerogenic peptide-based vaccination as a new therapeutic option for the prevention of RA and possible treatment of established disease.

Syfte och mål

We propose a tolerogenic peptide-based vaccination as a new therapeutic option for the prevention of RA and possible treatment of early/established disease. Tolerogenic vaccines represent a new class of vaccines designed to restore immunological tolerance, restore immune homeostasis, and thereby reverse autoimmune disease. The goal of this approach is to induce long-term, antigen-specific, inhibitory memory that blocks pathogenic T-cell responses without interfering with the protective function of the immune system.

Metod

The project is based on humanized mouse models with specific MHC haplotypes (referred to as HLA in humans), the strongest risk factor for RA. After several years of work, we have successfully established more physiological mouse models with full expression of human MHC class II molecules, mainly DRB10401 (associated with RA in Caucasians), DRB10405 (associated with RA and common in Asians) and DRB1*0402 (protective against RA ). We have also sorted two peptides for each *0401 and *0405 haplotype, to be used as tolerogenic vaccines according to our in-house protected protocol. We will use the delayed hypersensitivity (DTH) and collagen-induced arthritis (CIA) models in our humanized strains to test our vaccine candidates.

Betydelse för patienten

Currently, there is no specific treatment for RA and those available are used to reduce symptoms when the disease is already established. A safe, effective and specific vaccine, which targets antigen-specific T cells in the initial stages of the disease to prevent its progression, would help people living with RA to live longer and healthier lives. Therefore, our proposal will make it possible to develop a specific treatment that can be used in the initial stages to target and silence autoreactive T cells to prevent disease progression and improve quality of life for RA patients