A Vaccine for MS?
Shortly after I started blogging in 2007, I began to hear rumors in the MS community of a potential ‘MS Vaccine’ in development. A vaccine for MS? How do you vaccinate against something which isn’t contagious and for which we don’t know the exact cause? I wondered, would an MS vaccine work somewhat like the polio vaccine and basically eradicate the disease? Not quite.
The vaccines that we are most familiar with - to fight flu, polio, measles, tetanus, and more - contain a small amount of the offending bacteria or virus which has been weaken or killed (attenuated) so that it doesn’t make us sick, but it does tell our immune system, “hey, fight this invader now and any time it tries to attack again in the future.”
MS is an autoimmune disease in which our immune system begins to attack something we like having around in our bodies - cells related to myelin. Current MS disease-modifying therapies attempt to modulate the immune system to tamper these attacks. But as scientists learn more about the cells that are behaving badly - very specific populations of T-cells - they are working to develop therapies which target the behavior of those cells and only those cells.
That is what an ‘MS vaccine’ is all about. Teaching the immune cells to be more tolerant - “hey, lay off these myelin cells, they are our friends” - or to activate the immune system to create cells that help the “good guys” (regulatory T cells, or Tregs, anti-inflammatory cytokines IL-10, and others) to fight the rogue soldiers (pathogenic CD4+ and CD8+ T cells) that are attacking our myelin.
Many scientists around the world are experimenting with ways to modulate specific immune functions while preserving the immune system. The methods they have come up with are varied, from using genetically engineered DNA to antigen-specific therapy to attenuated T-cell vaccines loaded with proteins that attack myelin.
Last week, a research team at the Baylor Institute for Immunology Research (BIIR), studying dendritic cell vaccines for autoimmune diseases such as MS or type-1 diabetes, announced that early results from laboratory research initiated 3 years ago look promising.
"We discovered that DC-ASGPR, one of the receptors expressed on human dendritic cells, has novel functions to promote antigen-specific regulatory T cells that can efficiently suppress inflammatory responses," said led investigator Dr. SangKon Oh in a press release. "This prompted us to test our discovery in autoimmune diseases where antigens are known."
"Dr. Oh's approach is a very unique effort that would harness one's own immune system to suppress MS in an auto antigen-specific manner without disrupting other aspects of normal immunity," said Dr. Phillips, a member of the research team and neurologist whose work has focused on MS for more than three decades.
While the research is still in the early stages, results have been so positive that Dr. Oh said they are hopeful to begin a Phase I clinical trial in the next three years.
At the ACTRIMS-ECTRIMS Meeting in Boston, September 10-13, 2014, a research team from Russia, also studying the use of dendritic cells, modified with immature IL-10 cytokines, presented results from a small trial in three MS patients that accessed tolerability, safety, and immunological and clinical responses.
MS Vaccines in Clinical Development: A Brief Review
Tcelna (formerly known as Tovaxin) is an autologous T-cell vaccine that contains attenuated (killed) myelin-reactive T-cells (MRTC), taken from a patient’s own blood and combined with six myelin peptides (2 each from MBP, PLP, MOG). When injected back into the patient, Tcelna acts somewhat like a flu vaccine and activates the immune system to destroy this specific subset of autoreactive T-cells in circulation. Early reports from Phase I/II trials were promising, but results from Phase II and IIb clinical studies in relapsing-remitting MS and clinically isolated syndrome were not successful. A Phase II trial in secondary-progressive MS is ongoing.
NeuroVax is T-cell receptor (TCR) peptide vaccine, made from three peptides (BV5S2, BV6S5, and BV13S1) or pieces of protein that are overabundant in MS patients. In early clinical trials, NeuroVax produced a significant increase in TCR-specific T-cells, including increases in anti-inflammatory interleukin-10 (IL-10) cytokines and Foxp3+ regulatory T cells, in MS patients. NeuroVax received fast-track designation for SPMS from the FDA in March 2014 and clinical trials have been announced, but are not yet recruiting participants, to test NeuroVax in SPMS (two Phase IIb trials) and in pediatric MS (Phase I trial).
BHT-3009 is a tolerogenic (ie builds tolerance) genetically engineered DNA vaccine to myelin basic protein (MBP), a frequent target of the immune system in MS. In early clinical studies, a Phase I/II trial in RRMS and SPMS and a Phase II trial in RRMS, results show that BHT-3009 reduced signs of disease activity on MRI and was well tolerated, but no significant differences were seen regarding relapses compared to placebo. No ongoing or planned clinical trials are registered on clinicaltrials.gov.
RTL-1000 is an antigen specific therapy made of a recombinant T-cell receptor (TCR) ligand (RTL), a protein linked to myelin-oligodendrocyte-glycoprotein (MOG) peptide. RTL-1000 binds to antigen-presenting cells (APCs), inhibits T-cell activation, and induces T-cell tolerance. In mouse studies, it was shown to reverse clinical and histological disease and promote neural repair. In a Phase I dose-escalation study in 34 MS patients, single intravenous doses of up to 60 mg were well tolerated. No ongoing or planned clinical trials are registered on clinicaltrials.gov.
Researchers around the world continue to investigate similar therapies, such as MOG-DNA vaccines or T-cell vaccines created with a larger number of myelin peptides or vaccines containing specific viruses, to determine more efficacious anti-inflammatory mechanisms or additional therapeutic benefits such as neuroprotection or neural repair. The research is slow-going, so don’t hold you breath, but maybe someday there will be therapies that are so individualized to target only the rogue cells that wreak havoc in your immune system and only yours.1-5
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