Promising news in the world of autoimmune disease research. BioNTech SE announced today the publication of preclinical data on its novel mRNA vaccine approach against autoimmune diseases in the peer-reviewed journal Science.
The publication titled “A non-inflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis” summarizes the findings on the disease-suppressing effects of a non-inflammatory, nucleoside-modified mRNA vaccine in several clinically relevant mouse models of multiple sclerosis (MS).
Autoimmune diseases like MS represent conditions in which the immune system malfunctions and attacks healthy tissue or cells of the body. In MS, the inflammation causes the destruction of the protective myelin sheath that covers the nerve fibers. This damage disrupts the ability to transmit signals between nerve cells and the target tissue resulting in a range of neurological, sensory and motor symptoms that may differ greatly between individuals.
This first application of BioNTech’s mRNA technology in MSs represents a new modality in this indication and underlines BioNTech’s potential to leverage its proprietary mRNA platform.
In the study, a non-inflammatory nanoparticulate mRNA vaccine candidate encoding a MS-associated antigen was systemically applied to mice with experimental autoimmune encephalomyelitis (EAE), which represent clinically relevant mouse models of human MS. The mRNA vaccine candidate was designed to deliver the encoded autoimmune disease target antigen into antigen-presenting cells in the lymph nodes body-wide in a non-inflammatory context to enable systemic, immune tolerance-inducing antigen presentation in lymphoid tissues.
In all investigated EAE mouse models, the vaccine was able to prevent symptomatic disease or, in mice with early-stage disease, reduced further disease progression and restored motor functions. Pro-inflammatory effector T (Teff) cell infiltration in the brain and spinal cord and demyelination of the spinal cord was considerably reduced. These effects were achieved via development of disease-suppressing regulatory T (Treg) cells directed exquisitely against the antigen encoded by the mRNA vaccine. The Treg cells also executed a strong immunosuppressive bystander effect in the different MS mouse models, demonstrating that the Treg cells, once activated by their target antigen, can also suppress Teff cells against other antigens in the inflamed tissue in a complex disease setting. This is a crucial factor to also address polyclonal diseases based on multiple, partly unknown antigens, as well as inter-individual heterogeneity between patients.
Importantly, the preclinical vaccine candidate did not suppress functional immune responses against other, non-myelin antigens (e.g. influenza vaccine antigens), therefore addressing one of the key challenges in autoimmune treatment in the preclinical studies, the induction of an unspecific, systemic immune suppression. In addition, the vaccine candidate, even after repetitive application, did not induce formation of autoantibodies against the targeted antigen, another potential pitfall in current autoimmune therapies that could exacerbate disease. Overall, these initial results regarding the immune response together with the flexibility of the mRNA approach to target individual patient antigens indicate the potential of mRNA therapeutics to address highly complex and rare autoimmune disease indications.
The publication represents results of a collaborative study of scientists from BioNTech, TRON – Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, the Institute for Molecular Medicine at the University Medical Center of the Johannes Gutenberg University Mainz and the Research Center for Immunotherapy (FZI) at the Johannes Gutenberg University Mainz.