Dr Ellie Barnes

Research

Hepatitis C virus is currently a global epidemic infecting 170 million people worldwide and a significant issue in the United Kingdom, where 0.4 % of the population are infected. Many chronically infected patients silently develop complications of liver disease that include hepatocellular cancer, liver cirrhosis and liver failure. Current gold-standard treatments are suboptimal, fraught with side effects and often fail.

HCV vaccine development:
A major challenge for HCV vaccine development is the significant viral diversity both within the same host and between hosts –though parts of the viral genome are relatively conserved making these excellent T cell targets in the context of a T cell vaccine. Whilst a significant body of research has assessed T cell immunity to HCV genotype-1 infection very little is known about genotype-3a-now the dominant strain in the UK. Hope for a vaccine for HCV lies in the fact that after primary infection spontaneous viral eradication occurs in a significant minority of patients. The nature of the T cell response induced during this phase and HLA association studies demonstrate that T cell immunity critically affects the clinical outcome. More recently large human genome wide association studies have shown a major role for genetic polymorphisms linked to interferon-λ in both the spontaneous resolution and interferon-α induced viral eradication.

HCV vaccine clinical trials:
Phase-I clinical studies are currently underway in both healthy volunteers and in HCV infected patients at the John Radcliffe Hospital, Oxford, using viral vectored approaches. Early results using simian adenoviral vectors in collaboration with Okairos show real promise. Currently we are defining the relevance of T cell responses so generated to circulating virus within the host.

T cell immunity to genotype-3a infection:
A further focus of my laboratory related to vaccine development is the assessment of T cell immunity to genotype-3a infection in both acute infection when HCV specific T cell responses are readily detectable and in chronic infection where detection of responses often requires refined immunological techniques. Additional work is underway to define the complex interplay between interferon-λ, -α, and the adaptive immunity.

IgG4 systemic disease:
Other research interests include IgG4 systemic disease –a cause of biliary and pancreatic pathology of unknown aetiology, and the complexities of coagulopathy in liver disease.

Key Publications

Vaccination for hepatitis C Virus-closing in on an evasive target. J. Halliday, P. Klenerman, E Barnes, Exp Rev Vaccines-2011 May;10(5):659-7

Interferon lambdas: the next cytokine storm. Kelly C, Klenerman P, Barnes E. Gut. 2011 Apr 14. [Epub ahead of print]

Barnes E, Folgori A, Aston S. Phase I trial of a highly immunogenic T-cell vaccine for HCV based on novel adenoviral vectors from rare serotypes. Hepatology 50, 4(Suppl.), 105A (2009). Barnes E, Folgori A, Aston S. Phase I trial of a highly immunogenic T-cell vacine for HCV based on novel adenoviral vectors from rare serotypes. Hepatology 50, 4(Suppl.), 105A (2009)

Humphreys I, Fleming V, Fabris P, Parker J, Schulenberg B, Brown A, Demetriou C, Gaudieri S, Pfafferott K, Lucas M, Collier J, Huang KH, Pybus OG, Klenerman P, Barnes E. Full-length characterization of hepatitis C virus subtype 3a reveals novel hypervariable regions under positive selection during acute infection. J Virol. 2009 Nov;83(22):11456-66.

Rauch A, James I, Pfafferott K, Nolan D, Klenerman P, Cheng W, Mollison L, McCaughan G, Shackel N, Jeffrey GP, Baker R, Freitas E, Humphreys I, Furrer H, Günthard HF, Hirschel B, Mallal S, John M, Lucas M, Barnes E, Gaudieri S. Divergent adaptation of hepatitis C virus genotypes 1 and 3 to human leukocyte antigen-restricted immune pressure. Hepatology. 2009 Oct;50(4):1017-29.