Vaccine Fails to Reactivate Immunity to Hepatitis C Virus

Two papers recently published in Hepatology uncovered evidence of permanent immune system damage after hepatitis C virus (HCV) infection. The studies used a vaccine currently in clinical trials to attempt to restore immunity against HCV in animal models and humans with chronic HCV infection.

“In chronic HCV, CD8+ T cells are present, but they are not functioning,” explains Christopher Walker, PhD, director of the Center for Vaccines and Immunity at The Research Institute at Nationwide Children’s Hospital and lead author of the animal model study. “We wanted to see if the vaccine would illicit an immune response that would reactivate the CD8+ T cells against the virus.”

After vaccination, Dr. Walker’s team detected an increase in the T cells against the viral epitopes in the vaccine, but it could not restore the immune function of the T cells against circulating HCV.

“Our results suggest that HCV permanently damages the immune system,” says Dr. Walker, who is also a professor in the Departments of Pediatrics and Molecular Virology, Immunology, and Medical Genetics at The Ohio State University. “But we don’t know why.”

Similar results were observed by a team led by Ellie Barnes, PhD, professor of Hepatology and Experimental Medicine at Oxford University, in the first study of a potent HCV vaccine for chronically infected patients.

“Overall, the magnitude of HCV-specific T-cell responses following vaccination was markedly reduced compared to that in healthy volunteers,” says Dr. Barnes. “A potent T-cell vaccine alone is unlikely to restore T-cell immunity in chronically infected patients.”

The number of people infected with HCV has been steadily increasing over the past few years, according to the Centers for Disease Control and Prevention.

In the pediatric setting, infants are acquiring this silent infection through maternal transmission, while adolescents are developing it through IV drug use.

Unless individuals are tested due to risk factors, they might be unaware of the infection until years, sometimes decades, later when symptoms arise.

“If left untreated, the liver can produce 10 trillion new viruses a day,” Dr. Walker says. “The good news is that medications to treat HCV are very good, and more and more, a cure is possible. Unfortunately, even after a cure, many patients reacquire HCV after stopping treatment.”

Increasing infection and reinfection rates underscore the importance of an HCV vaccine.

“Although the vaccine is not being used as a therapy for HCV, there remains a real need for a preventative HCV vaccine,” Dr. Barnes says.

References:

1. Callendret B, Eccleston HB, Satterfield W, Capone S, Folgori A, Cortese R, Nicosia A, Walker CM. Persistent HCV replication despite priming of functional CD8+ T cells by combined therapy with a vaccine and direct acting antiviral. Hepatology. 2015 Oct 29. [Epub ahead of print]
2. Kelly C, Swadling L, Capone S, Brown A, Richardson R, Halliday J, von Delft A, Oo Y, Mutimer D, Kurioka A, Hartnell F, Collier J, Ammendola V, Del Sorbo M, Grazioli F, Luisa Esposito M, Di Marco S, Siani L, Traboni C, Hill AV, Colloca S, Nicosia A, Cortese R, Folgori A, Klenerman P, Barnes E. Chronic Hepatitis C Virus infection subverts vaccine induced T-cell immunity in humans. Hepatology. 2015 Oct 16. [Epub ahead of print]