Researchers at BioNTech were amongst the first to bring a vaccine against COVID-19, and perhaps this time, they got one against the neurodegenerative disease, Multiple Sclerosis (MS). Every year MS strikes about two million people across the world, especially in countries farther away from the Equator, out of which women are twice more likely to suffer than men. MS starts off almost asymptomatically with muscle spasms and blurry vision but may soon progress to paralysis and even death. The only treatment for MS till date was immunosuppression but that increases risk of other infections along with causing unwanted side effects like nausea, lack of appetite, increased hair growth, and hand trembling. It is high time to develop a vaccine for MS. By developing a modified messenger RNA (mRNA) vaccine, Krienke et al managed to stop disease progression in mice, hence holding promise in the clinic.
MS is a complex autoimmune disorder that leads to degeneration of the myelin sheath that wraps around neurons of the central nervous system (CNS), causing loss of nerve structure and function. MS involves a wide range of immune cells, but the main culprits are the autoreactive T cells. Due to reasons not yet clear, these T cells assume that protein fragments from the myelin sheath are foreign and hence must be destroyed. To this end, the autoreactive T cells travel to the CNS and cause inflammation that damage the nerves in the region. Although scientists identified the culprits, putting an end to them was almost impossible because these autoreactive T cells are often activated by not a single protein, but different protein fragments from the myelin sheath. This has made vaccine development difficult.
So, what did the BioNTech researchers do differently? In most vaccines (including the one made by BioNTech against SARS-CoV2), the more the inflammatory signals, the better the immune response. But for an autoimmune disease, a vaccine with lesser inflammatory signals is the way to go. The authors replaced Uridine, one of the four building blocks of mRNA, with a compound that can mimic it. Ergo, they achieved a modified mRNA; it is not sensed by Toll-like receptors on the dendritic cells – the antigen presenting experts. Hence, the delivered mRNA is translated into myelin peptides and presented to T cells but with the unnecessarily vigorous activation signals toned down. Now, instead of producing activated inflammatory T cells primed to destroy, a rather suppressive phenotype is induced. These suppressive T cells are our immune system’s main defense against immune rampage and are referred to as regulatory T cells (Tregs). Tregs release anti-inflammatory cytokines that can command other reactive immune cells to stop causing damage.
When mice suffering from an induced form of MS were treated with several doses of this modified mRNA vaccines at onset of the disease, its symptoms were ameliorated leading to complete recovery by stopping any further damage. At the cellular level, the researchers observed a large population of autoantigen specific Tregs traveling to the CNS and stopping autoreactive T cells. These Tregs could also execute “bystander tolerance”- they did not have to be specific to a particular myelin autoantigen to cause this protection- solving one of the biggest problems that MS vaccines have always faced.
But would this dampened immunity interfere with overall protection of the body against pathogens? Luckily not! The immune system primed responses against non-myelin antigens without any intervention from these specific Tregs which meant that the immune system still functioned like it should when under attack from pathogens.
BioNTech have revolutionized vaccine development by getting worldwide approval for the first ever mRNA vaccine against SARS-CoV-2. Although the technology is relatively new, our generation will be a spectator of more mRNA vaccines in near future and with them, a better understanding of the long-term effects of such vaccines. Will this modified mRNA vaccine against MS manage to extrapolate its promise from mice to humans? If successful, it would be another breakthrough for modern science, making MS the first autoimmune disease to have a cure and paving way to even more complex autoimmune diseases.
Article author: Kevin Merchant. Kevin is a MS student at LMU Munich, Germany, who is passionate about Immunology and writing. He aims to simplify latest research so that it becomes accessible to all.
Editor: Sutonuka Bhar. Sutonuka is a PhD candidate at the University of Florida. Her work focuses on host immune responses against viruses and bacterial membrane vesicles.
Check out Antibuddies’ new blog post “BioNTech Vaccine: A Ray of Hope for Multiple Sclerosis Patients”Tweet