🧠 Multiple Sclerosis Therapeutic Vaccine Tracker

Comprehensive tracking of Multiple Sclerosis (MS) therapeutic vaccine development targeting myelin antigens for immune tolerance, Epstein-Barr virus (EBV), and autoimmune pathways. MS affects 1 million US adults, 2.8 million globally. Autoimmune disease causing progressive neurological disability through CNS demyelination. Therapeutic vaccines aim to induce immune tolerance to myelin proteins, prevent relapses, slow disability progression. Multiple Phase 2/3 trials target myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), and EBV. DNA vaccines, peptide tolerance induction, and anti-viral approaches show promise. Complementary to disease-modifying therapies (DMTs) and lifestyle management.

⚠️ PROGRESSIVE NEUROLOGICAL DISABILITY:

Multiple Sclerosis affects 1 million Americans, 2.8 million globally. Autoimmune disease attacking CNS myelin causing vision loss, weakness, numbness, cognitive impairment, bladder dysfunction, progressive disability. Most common non-traumatic neurological disability in young adults (peak onset 20-40 years). Women affected 2-3x more than men. 85% start with relapsing-remitting MS (RRMS), eventually progressing to secondary progressive MS (SPMS) in 50%. Primary progressive MS (PPMS) 15%. Average life expectancy reduced 5-10 years. Current DMTs reduce relapses 30-70% but don't cure or fully prevent progression. Therapeutic vaccines offer hope for immune tolerance, disease modification.

🔬 Clinical Trial & News Resources:

📊 View all MS vaccine trials on ClinicalTrials.gov →
🌍 National MS Society →
🌍 NINDS MS Information →
🌍 MS International Federation →
📰 Latest MS Vaccine News (Google) →

MS Vaccines by Development Phase

US Cases (2.8M Globally)

85%

Start with Relapsing-Remitting MS

Vaccines in Development

🧬 Phase 2 Clinical Trials - Leading Candidates

ATX-MS-1467 (Myelin Peptide Vaccine)

Multi-myelin epitope tolerance induction - Most advanced

Phase 2

Developer Apitope Technology

Technology 4 myelin peptides (MBP, PLP, MOG)

Mechanism Immune tolerance via regulatory T cells

Phase 1 Results Safe, tolerogenic effects

Target Secondary progressive MS (SPMS)

Trial Info ClinicalTrials.gov

Developer: Apitope Technology (UK) | Partner: Merck KGaA | Trials: View Phase 2 trials

Details: ATX-MS-1467 contains four myelin peptides representing immunodominant epitopes from myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG) - the three primary targets of autoimmune attack in MS. Peptides derived from sequences 85-99 of MBP, 139-151 of PLP, and others. Delivered intradermally to induce immune tolerance through presentation to regulatory T cells (Tregs). Unlike conventional vaccines activating immunity, this INDUCES tolerance - "teaching" immune system to ignore myelin. Phase 1 trials (healthy volunteers and RRMS patients) showed excellent safety, no disease flares, evidence of Treg induction and reduced myelin-reactive T cell responses. Phase 2 ETIMS trial (secondary progressive MS, 60 patients) evaluating efficacy: MRI lesions, brain atrophy, clinical progression. Monthly injections for 6 months. Primary endpoint: MRI measures of disease activity. Results expected 2025-2026. If successful, could be first tolerance-inducing vaccine for progressive MS - population with limited treatment options (only siponimod, ocrelizumab approved).

Strategy & Rationale: MS pathogenesis: autoreactive T cells cross blood-brain barrier, recognize myelin proteins as "foreign," trigger inflammation, demyelination, axonal damage, disability. Current DMTs suppress entire immune system (infection risk) or deplete B/T cells. ATX-MS-1467 offers antigen-specific tolerance - selectively "turning off" myelin-reactive cells while preserving normal immunity. Advantages: No broad immunosuppression, restore natural tolerance mechanisms, potentially disease-modifying (not just symptom control), applicable to progressive MS where inflammation less prominent but ongoing neurodegeneration occurs. Challenges: Individual HLA variability (peptides bind specific HLA alleles - may not work for all patients), timing (tolerance easier to induce early disease vs. established), proving efficacy in slowly progressive disease (requires long trials, large sample sizes).

EBV Vaccine (Anti-Viral Approach)

Targeting Epstein-Barr virus - MS trigger

Phase 2

Developers Moderna

Technology mRNA encoding EBV antigens

Rationale EBV strongly linked to MS risk (32x)

Goal Prevent MS onset, slow progression

Developer: Moderna Inc. | Research: Stanford, Harvard

Background - EBV-MS Connection: Groundbreaking 2022 Science study (10 million US military personnel, 20-year follow-up): EBV infection increased MS risk 32-fold. Virtually all MS patients EBV-positive (99.5% vs. 94% general population). EBV infection precedes MS onset by years (median 5-10 years). Proposed mechanism: Molecular mimicry - EBV nuclear antigen 1 (EBNA1) shares sequence homology with myelin proteins. Anti-EBNA1 antibodies cross-react with CNS myelin, triggering autoimmunity. EBV-infected B cells migrate to CNS, perpetuate inflammation. Strongest environmental risk factor identified.

Vaccine Development: Moderna mRNA-1189 encodes EBV glycoprotein gp350, gH/gL complex, and EBNA proteins for broad immunity. Aims to prevent EBV infection (primary prevention of MS in at-risk individuals) OR reduce EBV viral load in MS patients (therapeutic - may slow progression if chronic EBV reactivation drives disease). Phase 1 safety trials completed. Phase 2 evaluating: (1) Prophylactic efficacy in EBV-seronegative adolescents; (2) Therapeutic effects in early RRMS. Unprecedented approach: preventing MS by targeting upstream viral trigger rather than autoimmune process itself. If successful, could prevent significant proportion of MS cases globally. Challenge: proving MS prevention requires decades-long trials. Intermediate endpoints: EBV infection rates, anti-EBNA1 antibody titers, MRI activity in therapeutic arm.

🧪 Phase 1 Clinical Trials

BHT-3009 (DNA Vaccine)

DNA plasmid encoding myelin basic protein

Phase 1

Developer Bayhill Therapeutics

Technology DNA plasmid - MBP gene

Mechanism Tolerance via intramuscular DNA

Developer: Bayhill Therapeutics

Description: DNA vaccine encoding full-length myelin basic protein. Intramuscular injection leads to MBP expression in muscle, presentation to immune system in tolerogenic context (absence of inflammation), inducing regulatory responses. Earlier Phase 2 trials showed trends toward reduced relapses, MRI activity but didn't meet primary endpoints. Reformulated for Phase 1 with improved plasmid design, dosing. Concept: gene-based tolerance induction potentially more sustained than peptide vaccines.

Additional Phase 1 Candidates (2)

Novel myelin tolerance approaches

Phase 1

Candidates: (1) Altered Peptide Ligands (APLs) - Modified myelin peptides inducing Th2 shift (anti-inflammatory) rather than Th1 (pro-inflammatory); (2) Nanoparticle-encapsulated myelin antigens - Deliver to tolerogenic APCs (antigen-presenting cells) in liver/spleen for systemic tolerance.

Institutions: NIH/NINDS, Northwestern University

🔬 Preclinical Development

Preclinical Platforms (4)

Next-generation tolerance strategies

Preclinical

Approaches: (1) Antigen-coupled nanoparticles - Biodegradable particles presenting myelin peptides + immunomodulatory molecules (TGF-β, IL-10) to induce Tregs; (2) Gut mucosal tolerance - Oral myelin antigens activating gut immune tolerance mechanisms; (3) Combination vaccines - Myelin tolerance + B cell depletion + remyelination factors; (4) Personalized vaccines - Based on individual HLA type, myelin epitope spreading patterns.

Research Centers: NIH/NINDS, UCSF, Northwestern, Stanford, University of Zurich

⚠️ Discontinued Programs - Learning from Failures

Copaxone (Glatiramer Acetate) - Success Story

Actually approved - not a true vaccine but similar mechanism

Approved DMT

Note: Copaxone approved 1996 for RRMS. Random polymer of four amino acids mimicking myelin basic protein. Mechanism: induces Th2 shift, Treg activation, similar to tolerance vaccines. Daily injection. Modest efficacy (30% relapse reduction) but excellent safety. Proves concept that antigen-specific immunomodulation works in MS. Modern vaccines aim for superior efficacy with less frequent dosing.

Failed Myelin Vaccines

Early peptide vaccines

Discontinued

MBP8298 (Altered Peptide Ligand): Phase 3 trial failed - no significant benefit vs. placebo in SPMS. Issue: heterogeneity of MS (multiple epitopes involved, not just one peptide). Single peptide insufficient for broad population.

Oral Myelin: Phase 3 trials of oral myelin for gut tolerance failed. Concept sound but inadequate antigen delivery/dosing. Led to modern nanoparticle approaches with better bioavailability.

Lessons: Multi-epitope vaccines superior to single peptides. Patient selection critical (HLA matching). Early intervention better than late-stage progressive disease. Long trials needed (slow progression). Biomarkers essential (MRI, neurofilament light chain).

📊 Disease Burden & Treatment Landscape

Multiple Sclerosis - Complex Autoimmune Disease

Epidemiology: 1 million US, 2.8 million globally. Prevalence increasing (better diagnosis, true increase unclear). Women:Men ratio 2-3:1. Peak onset 20-40 years (young adults). More common in northern latitudes (vitamin D hypothesis). Caucasians higher risk than other ethnicities. Strong genetic component: HLA-DR15 allele increases risk 3-fold, but concordance in identical twins only 30% (environment matters).

Clinical Course: 85% start with Relapsing-Remitting MS (RRMS) - discrete attacks (relapses) with full/partial recovery. Symptoms: vision loss (optic neuritis), numbness/tingling, weakness, balance problems, bladder dysfunction, cognitive impairment, fatigue. After 10-15 years, 50% transition to Secondary Progressive MS (SPMS) - gradual worsening without clear relapses. 15% have Primary Progressive MS (PPMS) - steadily worsening from onset, no relapses, older age at onset, worse prognosis.

Pathophysiology: Autoimmune attack on CNS myelin. Autoreactive CD4+ T cells (Th1, Th17) cross blood-brain barrier, recognize myelin antigens (MBP, PLP, MOG), trigger inflammation. B cells produce antibodies against myelin, activate complement. Macrophages/microglia phagocytose myelin. Result: demyelination → impaired nerve conduction → symptoms. Axonal damage occurs early, accumulates → irreversible disability. Lesions (plaques) visible on MRI in brain, spinal cord, optic nerves.

Current Treatment - DMTs

First-Line (Moderate Efficacy): Interferons (Avonex, Rebif, Betaseron) - 30% relapse reduction, injection site reactions, flu-like symptoms. Glatiramer acetate (Copaxone) - 30%, similar to interferon but different mechanism. Dimethyl fumarate (Tecfidera) - oral, 50%, GI side effects. Teriflunomide (Aubagio) - oral, 30%, liver monitoring.

Higher-Efficacy (More Risks): Natalizumab (Tysabri) - 70% reduction, monthly infusion, PML risk (brain infection). Ocrelizumab (Ocrevus) - 50%, B-cell depletion, infusion reactions. Alemtuzumab (Lemtrada) - 50-70%, lymphocyte depletion, autoimmune complications. Cladribine (Mavenclad) - oral pulse dosing, immunosuppression. Siponimod (Mayzent) - SPMS approved, modest benefit.

Limitations: All immunosuppressive (infection risk). Don't induce tolerance (stop drug → disease returns). Limited efficacy in progressive MS. Expensive ($80,000-100,000/year). Side effects common. Don't repair myelin or reverse damage. Reduce inflammation/relapses but don't cure.

Therapeutic Vaccines - Paradigm Shift Potential

Unique Value: Antigen-specific tolerance (preserve normal immunity). Potentially disease-modifying (restore tolerance, not just suppress). Less frequent dosing than daily/monthly DMTs. Lower infection risk (no broad immunosuppression). Could be additive/synergistic with DMTs. Applicable to progressive MS (tolerance may slow neurodegeneration).

Target Populations: Early RRMS (before extensive damage), CIS (clinically isolated syndrome - first attack), at-risk individuals (high genetic risk, EBV+), SPMS with ongoing MRI activity, as add-on to DMTs to improve efficacy.

Realistic Expectations: Won't reverse disability (axons don't regenerate). Best used early before irreversible damage. May slow progression 20-40%. Combination with remyelination strategies (opicinumab, clemastine) needed for repair. EBV vaccine most exciting for prevention in coming generations.

Challenges: MS heterogeneity (multiple epitopes, disease subtypes). HLA restriction (vaccines work for specific HLA types only). Proving efficacy (progressive MS slow, requires long trials). Regulatory precedent (no approved tolerance vaccine for autoimmune disease). Timing critical (tolerance harder once disease established). Epitope spreading (new epitopes targeted over time → vaccine cocktails needed).

Future 2030-2040: EBV vaccine prevents 30-40% of MS cases (population-level vaccination). Multi-epitope tolerance vaccines standard add-on to DMTs in early RRMS. Personalized vaccines based on HLA typing, epitope mapping. Combination: tolerance vaccine + B-cell depletion + remyelination therapy. MS becomes chronic manageable disease like diabetes, not progressive disability. Wheelchair use from MS reduced 50%+.