Vaccine for Immune Regulation & Transplant Survival

A vaccine activated and encouraged subtype of CD8 T cells, which are often thought to stimulate immune system responses, may really be regulating the immune system by suppressing immune cells, triggering self-destructive responses and organ graft rejection.

In collaboration with researchers from the Dana-Farber Cancer Institute, a team led by researchers from the Department of Medicine and the Transplant Research Center at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, developed a vaccine in preclinical models to promote immune regulation. This vaccination stimulates CD8 T regulatory cells by using synthetically modified natural peptides. The researchers revealed, using a mouse model, that self-peptides supplied by a specific class of major histocompatibility complexes mark dangerous immune cells for the body’s own regulatory CD8 Tregs to attack and remove.

The vaccine activated and encouraged regulatory T cells, which in turn kept dangerous cells at bay. These cells are critical for immune response maintenance and inflammation prevention. The scientists discovered that the proposed vaccine increases allograft survival in mice and tested anti-allograft immunity on mismatched kidney transplants. An equivalent route in humans was also discovered, hinting that this research could benefit persons suffering from autoimmune diseases or organ transplant recipients.

This new vaccine promotes immune regulation that treats autoimmunity and prolongs kidney allograft survival in mice. Our research identifies an analogous pathway in humans that we hope to target soon.”

Jamil R. Azzi, MD, PhD, co-corresponding author, Brigham’s Transplant Research Center

“Identification of human T cell receptors homologous to the mouse model tested may form the basis of a novel and effective treatment for disorders that reflect excessive or dysregulated immune responses.” This work was done in collaboration with co-corresponding author, Harvey Cantor MD, of the Dana-Farber Cancer Institute.