Join our email list!

Get daily updates delivered to your inbox
Thank you for subscribing

BioNTech Vaccine Treats MS in Mice Without Dampening Immune System

BioNTech Vaccine Treats MS in Mice Without Dampening Immune System
4.8
(213)

BioNTech’s experimental non-inflammatory vaccine — designed to dampen the abnormal immune responses seen in multiple sclerosis (MS) against myelin — delayed the onset and lessened the severity of symptoms in a mouse model of MS, a study reports.

Importantly, treated mice showed no signs of overall immune suppression, suggesting that this type of therapy may overcome the downsides associated with current immunosuppressive therapies for MS.

These data support advancing this vaccine, and possibly bringing it into testing in patients.

The study, “A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis,” was published in the journal Science.

MS is an autoimmune disease in which the immune system mistakenly attacks myelin, the fatty protective sheath that covers nerve fibers. As such, the main goal in treatment development for MS and other autoimmune conditions is to specifically suppress the cells that drive these immune attacks, without promoting overall immune suppression.

However, this has proven challenging. Current MS disease-modifying therapies promote, in one way or another, a general suppression of the immune system or of its key players, potentially impairing immune responses against real threats and increasing the risk of infections.

According to BioNTech, its experimental, non-inflammatory vaccine may revolutionize MS treatment by re-educating regulatory T-cells (Tregs) — a type of immune cell that typically dampens immune and inflammatory responses — to tolerate myelin-associated proteins and suppress immune reactions against them.

Notably, this vaccine differs from conventional vaccines in two main aspects. First, instead of stimulating a person’s immune system to recognize, memorize, and readily fight specific microbes or molecules, it promotes immune tolerance to a particular molecule.

Secondly, it does so by delivering messenger RNA (mRNA) — the intermediate molecule generated from DNA that serves as a template for protein production — rather than protein fragments to cells. This means that after entering cells, the mRNA containing the instructions to produce a specific protein is used by the cell to produce that protein, which then is “shown” to immune cells.

In the specific case of MS, the vaccine’s mRNA was designed to contain the instructions to produce a myelin-specific protein mistakenly targeted by immune cells in MS, and modified so as to be less likely to promote immune responses.

The therapy uses tiny particles to deliver the mRNA to dendritic cells, a type of immune cell that presents molecules to other immune cells, including Tregs, promoting immune tolerance when in a non-inflammatory context — the situation intended with this vaccine.

Researchers at BioNTech, along with colleagues at research organizations and institutes of the Johannes Gutenberg University Mainz, in Germany, tested the effects of the mRNA vaccine in several mouse models of MS based on the experimental autoimmune encephalomyelitis (EAE) model.

Results from all evaluated mouse models showed that the vaccine prevented disease development or, in mice with early stage disease, halted its progression and restored the animals’ motor function.

Treated mice also showed considerably few pro-inflammatory immune cells in the brain and spinal cord, as well as lesser myelin damage.

Further analyses showed that these benefits were associated with an expansion of a specific population of Tregs suppressing immune cells and responses against the myelin-specific molecule encoded by the mRNA vaccine.

Notably, these Tregs also promoted the suppression of T-cells targeting myelin-specific molecules not included in the vaccine’s formulation — a bystander effect. This suggests that Tregs can also block the activity of immune cells “against other [molecules] in the inflamed tissue in a complex disease setting,” BioNTech stated in a press release.

This is crucial to address diseases in which the abnormally targeted molecules are partly unknown and in which there are disease-associated differences between patients, the researchers noted.

Moreover, treated mice displayed no signs of general immune suppression and showed adequate immune responses against vaccine-delivered flu protein fragments, suggesting that the mRNA vaccine did not result in overall immune system impairment.

In addition, even after repetitive vaccine administration, there were no signs of immune responses against the targeted molecule, highlighting that its presentation to Tregs was promoting immune tolerance only, rather than immune responses that could worsen the disease.

“Overall, these initial results regarding the immune response together with the flexibility of the mRNA approach to target individual patient [target molecules] indicate the potential of mRNA therapeutics to address highly complex and rare autoimmune disease indications,” the company noted in its release.

BioNTech has extensively used its mRNA technology to develop candidate therapies for several types of cancer and for COVID-19 infection — for which the company’s mRNA vaccine Comirnaty, co-developed with Pfizer, was recently approved. This vaccine, however, represents the first application of such technology for the treatment of autoimmune diseases.

Marta Figueiredo holds a master’s in evolutionary and developmental biology and a PhD in biomedical sciences from the University of Lisbon, Portugal. Her research is focused on the role of several signaling pathways in thymus and parathyroid glands embryonic development.
Total Posts: 1,053
Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
×
Marta Figueiredo holds a master’s in evolutionary and developmental biology and a PhD in biomedical sciences from the University of Lisbon, Portugal. Her research is focused on the role of several signaling pathways in thymus and parathyroid glands embryonic development.
Latest Posts
  • overall cost of DMTs
  • MS therapies
  • myelin
  • Kesimpta

How useful was this post?

Click on a star to rate it!

Average rating 4.8 / 5. Vote count: 213

No votes so far! Be the first to rate this post.

As you found this post useful...

Follow us on social media!

We are sorry that this post was not useful for you!

Let us improve this post!

Tell us how we can improve this post?