Study Examines Ways to Restore Immunity to Chronic Hepatitis C Infection

The hepatitis C virus (HCV) attacks the immune system, stopping T cells from functioning. Using animal models, researchers found a way to block a protein called programmed cell death 1 (PD-1) that helps the virus thrive, thus restoring immune function so that the body can fight infection. PD-1 is a protein that helps regulate the immune system. It can turn off immune responses when an infection is under control. HCV manipulates the PD-1 off switch, causing T cells to lose their ability to fight the infection and enabling HCV to persist in the liver.

Scientists at the Research Institute at Nationwide Children’s Hospital and Emory University treated animal models with persistent HCV infection with doses of an anti-PD-1 antibody. One animal showed an intense increase in HCV-specific T cell activity in the liver and a significant decrease in viral load. The animal had more HCV-specific T cells in the liver before therapy, which means that treatment success might depend on the number of HCV-specific T cells in the liver prior to treatment. Also, PD-1 antibody helped recovery of the CD4+ T cells, helper cells that promote development of killer T cells (CD8+ cells) that target and destroy virus-infected liver cells.

The researchers suggested that the T cells were in the liver for years but were undetectable before treatment and only expanded after treatment. According to Christopher Walker, PhD, senior author of the study and director of the Center for Vaccines and Immunity at Nationwide Children’s Hospital, results suggested that anti-PD-1 antibodies were effective in treating HCV and other persistent human viral infections. If T-cell response to the initial infection was good, but not enough to clear the virus, the patient might respond to PD-1 blockade years later. Those whose initial T cell response was limited and weak might not respond to PD-1 blockade.

The full report, “Immunotherapy of Chronic Hepatitis C Virus Infection with Antibodies Against Programmed Cell Death-1 (PD-1)” was published online in the journal Proceedings of the National Academy of Sciences (2013; doi: 10.1073/pnas.1312772110).