Tracking Teplizumab (Tzield) & Immune Tolerance Vaccines
Type 1 Diabetes (T1D) is an autoimmune disease where the immune system destroys insulin-producing beta cells in the pancreas, affecting 1.6 million Americans and 9 million globally. Unlike traditional vaccines that prevent infection, T1D vaccines are therapeutic immunotherapies that delay or prevent disease onset by inducing immune tolerance. In November 2022, the FDA approved Teplizumab (Tzield) - the first disease-modifying therapy for T1D, delaying clinical diagnosis by ~3 years (median 32 months) in at-risk individuals. This breakthrough represents decades of research into autoimmune disease prevention. This tracker monitors approved therapies, prevention vaccines for at-risk individuals (those with T1D autoantibodies), reversal vaccines for recent-onset T1D, and immune tolerance strategies including oral insulin, GAD65, and beta cell vaccines.
Developer: Provention Bio / Sanofi
Platform: Anti-CD3 monoclonal antibody immunotherapy
Target: At-risk individuals (stage 2 T1D: multiple autoantibodies + dysglycemia but no clinical symptoms)
Mechanism: Targets CD3 on T cells, inducing immune tolerance and preserving beta cell function
Breakthrough Efficacy: Delayed onset of clinical T1D by median 32 months (nearly 3 years) vs. placebo in Phase 3 trial
Administration: 14-day IV infusion course (daily infusions)
Significance: First FDA-approved therapy to delay T1D onset. Paradigm shift from treating disease to preventing it in at-risk individuals.
Status: Available in USA. Recommended for at-risk individuals aged 8+. Requires screening for T1D autoantibodies.
Developer: Diamyd Medical
Platform: Autoantigen vaccine - GAD65 (glutamic acid decarboxylase) with alum adjuvant
Strategy: Induce immune tolerance by exposing immune system to GAD65 (beta cell protein) to stop autoimmune attack
Target: Recent-onset T1D and at-risk individuals
Results: Phase 2 trials showed C-peptide preservation in certain HLA genotypes (particularly HLA DR3-DQ2)
Status: Phase 3 trials in Europe (DIAGNODE-3) enrolling 330 participants with recent-onset T1D and specific HLA type
Developer: Multiple groups (Type 1 Diabetes TrialNet, others)
Platform: Oral or intranasal insulin to induce mucosal tolerance
Rationale: Exposing immune system to insulin via gut/nasal mucosa may induce tolerance without systemic effects
Target: Primary prevention in high-risk children (genetically predisposed, autoantibody-positive)
Studies: Pre-POINT (early) and POInT (primary prevention) trials ongoing in children
Status: Phase 2 trials evaluating safety and immune markers in at-risk children
Developer: Imcyse / multiple academic groups
Platform: Synthetic peptide derived from proinsulin
Strategy: Antigen-specific immunotherapy inducing regulatory T cells (Tregs) that suppress autoimmune attack
Target: Recent-onset T1D to preserve remaining beta cells
Status: Phase 2 trials evaluating C-peptide preservation
Developer: Massachusetts General Hospital (Faustman Lab)
Platform: Bacillus Calmette-Guérin (TB vaccine) repurposed for T1D
Mechanism: Hypothesized to "reset" immune system via TNF induction, potentially reversing autoimmunity
Target: Long-standing T1D (>5 years diagnosis)
Controversial: Mixed results - some studies show modest C-peptide improvement, others show no benefit
Status: Phase 2 trials ongoing with larger cohorts
Developer: Academic consortia
Platform: Combination of anti-thymocyte globulin (ATG) + granulocyte colony-stimulating factor (GCSF)
Strategy: Deplete autoreactive T cells (ATG) then promote regulatory T cells (GCSF)
Target: New-onset T1D
Status: Early trials showing promise in C-peptide preservation
Developer: Multiple academic institutions
Platform: Autologous dendritic cells modified to induce tolerance
Strategy: Patient's dendritic cells loaded with beta cell antigens, modified to promote tolerance rather than immunity
Target: Recent-onset T1D
Status: Phase 1 safety trials
Teplizumab's FDA approval marks a paradigm shift from treating T1D after diagnosis to preventing it before symptoms appear. The disease has three stages: Stage 1 (2+ autoantibodies, normal glucose), Stage 2 (autoantibodies + dysglycemia), Stage 3 (clinical symptoms requiring insulin). Teplizumab targets Stage 2, delaying progression to Stage 3. Key challenges: (1) Screening: Most at-risk individuals unidentified (requires autoantibody testing), (2) Access: 14-day IV infusion is intensive and expensive, (3) Duration: Protection wanes over time - disease still eventually progresses, (4) Side effects: Transient lymphopenia, rash (manageable but concerning). Future directions: oral/intranasal vaccines for primary prevention in children, combination therapies (antigen + immunomodulation), beta cell regeneration alongside immune tolerance, and identifying best responders via biomarkers. The ultimate goal: prevent T1D entirely, not just delay it.