Director of Immunobiology/Associate Professor of Medicine Massachusetts General Hospital/Harvard Medical School Charlestown, Massachusetts, United States
Abstract Text: The bacillus Calmette-Guerin (BCG) vaccine is being tested in clinical trials for treatment of diverse forms of autoimmunity. Multiple clinical protocols in type 1 diabetes (T1D) are underway at our institution testing various aspects of BCG’s ability to lower HbA1c, reduce insulin requirements and regulate blood sugars: 1) Ten-year follow up of a Phase I study of BCG vaccination in adults with longstanding T1D to study the durability of lowered HbA1c values after treatment; 2) Randomized, double-blinded Phase II clinical trial testing the BCG vaccine in adults with longstanding T1D; 3) Radiologic study to identify organs and organ systems with higher sugar utilization after BCG treatment; 4) Study in adults with longstanding T1D evaluating two versus 6 doses of BCG over 5 years of observation; 5) A multicenter clinical trial of adolescents with >2 years since T1D diagnosis to evaluate potential benefits of BCG vaccination. Immune and metabolic mechanisms accounting for BCG’s durable effects include epigenetic modulation of glucose signaling pathways, reset of the Treg cellular subset and correction of underlying aerobic glycolysis defects in T1D lymphocytes, leading to regulated glucose control. To date, 295 of 500 planned patients are enrolled, including 272 BCG-vaccinated patients. Global studies show that the impact of multi-dose BCG vaccination in multiple sclerosis (MS) and T1D is seen with at least 2 years of follow up and that the effects appear durable without further treatment in both MS and T1D to 5+ years. BCG vaccine therapy may offer a safe, affordable intervention in longstanding autoimmunity.
