MS vaccines: Thinking outside the box for new treatments

At its heart, multiple sclerosis is believed to occur when rogue immune cells attack myelin – a fatty coating that surrounds nerve cells in the brain and spinal cord. But what if these deviant immune cells could be taught to leave myelin alone? Or the immune system reprogrammed to fight these cells off?  This is what researchers are hoping to do as they bring an age-old technology, vaccines, to bear in the treatment of MS.

When you think of vaccination, your mind probably goes to the shots you received as a child that were meant to protect you against certain bacterial or viral infections. Today, scientists are trying to adapt this same technology (with a few tweaks of course) to help stop autoimmune attacks.  In the last few years a number of MS-focused vaccines have shown promising results in early phase clinical trials, and with each success the technology is closer than ever to offering a viable treatment option.

Source: James Gathany [Public domain], via Wikimedia Commons

Source: James Gathany [Public domain], via Wikimedia Commons

Before we get any further, let’s remind ourselves of how vaccines work. In general, vaccines contain small harmless fragments of a virus or bacteria. When these bits and pieces are injected into the body, they trick the immune system into “thinking” there is an infection. A defense is mounted and the virus or bacteria is destroyed by the body’s immune system.  In the process, the immune system creates a memory of the event, keeping itself primed for future encounters with the virus or bacteria. As you know, vaccines are administered early in life and at various periods of time throughout one’s life, to ensure that the immune system is prepared to fight infection later on.

In contrast, MS-focused vaccines are not loaded with bacteria or viruses. Rather, they may contain small fragments of myelin, myelin-reactive cells (immune cells that attack myelin) or, in some cases, large numbers of weakened myelin-reactive cells. Depending on its makeup, the vaccine can either teach hostile immune cells to leave the body’s myelin alone or turn the immune system against these rogue cells (treating them almost like an infection). In both scenarios the vaccine is intended to blunt the autoimmune response and allow the central nervous system time to recover.

 

MS vaccines in practice

So what’s out there? Just this past month, a team of researchers from Russia reported positive results from phase 1 and 2 trials with an experimental vaccine, Xemys, developed by pharmaceutical company PJSC Pharmsynthez (1). The vaccine is meant to treat individuals with relapsing remitting and secondary progressive MS who no longer respond to first-line immunosuppressive drugs such as interferon beta.  Following 6 weeks of injections, just over 80% of the study’s participants reported being relapse-free. While the phase 2 trial was relatively small in scope (20 participants over 18 weeks total), the results were promising, with Xemys expected to enter Phase 3 trials in the near future.

As to how it works, it’s probably easiest to think of Xemys as an allergy shot for myelin. Participants are injected with low doses of an “allergen”, in this case small fragments of a protein found in myelin.  The purpose of this type of vaccine is to create antigen-specific tolerance, which is a unique way to reprogram the immune system to tolerate and thus steer away from myelin.

Xemys is just one of several MS-focused vaccines being studied. For example, researchers, including Dr. Amit Bar-Or from the Montreal Neurological Institute, published positive results from early-stage clinical trials testing the safety and effectiveness of a vaccine called BHT-3009, meant to treat individuals living with relapsing remitting and secondary progressive forms of MS (2,3).   Unlike Xemys, which contained fragments of a myelin specific protein, BHT-3009 actually held DNA that coded for the entire myelin protein.

NeuroVax – a vaccine developed by Immune Response BioPharma, Inc. and currently in phase 2 trials for progressive MS – contains proteins commonly found on the surface of myelin-reactive immune cells (4). This vaccine is designed to turn a person’s immune system against the rogue cells,  dampening  the inflammatory response against myelin in the process.

Another vaccine, Tcelna (currently under development by Opexa  Therapeutics, Inc.) is part of an emerging trend of “personalized treatments” – the vaccine is specifically formulated for every individual who receives it. Myelin-reactive immune cells are collected from a person’s blood and grown in culture.  The cells are then exposed to radiation (which renders them harmless) before being administered to the original donor.  Reintroduction of these harmless myelin-reactive immune cells triggers an immune response, with the cells now seen by the person’s immune system as as “invaders”. The immune system then seeks out and shuts down similar myelin-reactive immune cells still present in the person’s body.

Phase 2 trials for Tcelna have been successfully completed in people with relapsing remitting MS, with results suggesting a positive improvement to disability scores for invididuals with a more active form of the disorder (one or more relapses every year) (5,6). The vaccine has received Fast Track approval by the US Food and Drug Administration (meant to expedite a drug’s development) for trials in secondary progressive MS.

 

The future of MS vaccines

In theory, vaccines hold a twofold advantage over currently approved disease-modifying therapies.  Whereas many immunosuppressive drugs target both good and bad immune cells in the body, vaccines specifically target only the cells that react against myelin,  leaving the rest of the immune system relatively intact to fight infections. For this reason many scientists believe vaccine-based treatments can minimize the possibility of adverse side effects while maximizing benefits.  Vaccines also represent a push towards a life-long solution: a working vaccine aims to “fix” the problem at its root, reprogramming the immune system for the long-term.

However, while vaccines are meant to temper the immune system, they are not designed to actively repair pre-existing myelin damage. There is the possibility that with the immune system calmed, the brain and spinal cord can naturally regenerate damaged myelin through a process known as remyelination. Unfortunately, for reasons that are still not entirely understood, remyelination often stalls or is impaired in people living with MS. The research community acknowledges that therapeutic strategies will need to modulate the immune system as well as enhance the central nervous system’s innate ability to repair damage. This realization has driven scientists to look at repurposing or developing new non-vaccine based drugs to overcome remyelination failure and encourage myelin regrowth.  When coupled with myelin tolerating technology like vaccines, the hope is for a more complete therapy for those living with MS.

While vaccines are not a silver bullet, they do offer a more refined and targeted approach to control an aggressive immune system.  Many vaccines, such as Xemys, are being developed to meet the needs of individuals who do not, or no longer, respond to first-line drug treatments.  They are indicative of the more personalized approach to medicine that many researchers and clinicians are beginning to take. New treatment options allow scientists and clinicians to tailor treatments to individuals, a critical factor in a disorder experienced by so many people in different ways. Some vaccines, such as Tcelna, take this personalized treatment to the next level, using a person’s own immune cells.

Although vaccines are still in early development in terms of their application in MS, they along with recent breakthroughs in stem cells represent an era of fully personalized medicine that may be the next major step in MS treatment.

Any questions or comments? Leave them below.

 

References

  1. Belogurov Jr A et al. (2016) CD206-Targeted Liposomal Myelin Basic Protein Peptides with Multiple Sclerosis Resistant to First-Line Disease-Modifying Therapies: A First-in-Human, Proof-of-Concept Dose-Escalation. DOI: 10.1007/s13311-016-0448-0
  2. Garren H et al. (2008) Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis. Annals of Neurology. 63(5): 611-20.
  3. Bar-Or A et al. (2007) Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial. Archives of Neurology. 64(10):1407-15.
  4. Vandenbark AA et al. (2008) Therapeutic vaccination with a trivalent T-cell receptor (TCR) peptide vaccine restores deficient FoxP3 expression and TCR recognition in subjects with multiple sclerosis. 123(1):66-78.
  5. Fox E et al. (2012) A randomized clinical trial of autologous T-cell therapy in multiple sclerosis: subset analysis and implications for trial design. Multiple Sclerosis Journal. 18(6):843-52.
  6. Loftus B et al. (2009) Autologous attenuated T-Cell vaccine (Tovaxin®) dose escalation in multiple sclerosis relapsing-remitting and secondary progressive patients nonresponsive to approved immunomodulatory therapies. Clinical Immunology. 131(2):202-15.

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