Hepatitis C Vaccine Programme

Programme Leaders: Prof Paul Klenerman and Prof Ellie Barnes


Hepatitis C virus infects around 170 million people globally and is a major cause of liver disease, leading to progressive liver scarring and liver cancer. No vaccine currently exists, and the current treatment is only partially effective, as well as being expensive and associated with substantial side effects. About a quarter of those initially infected clear the virus spontaneously, although the majority become persistently infected.

Hepatitis C researchers
Researchers in the Hepatitis C Vaccine Programme: Rachel Townsend, Anthony Brown, Leo Swadling, Ellie Barnes and Christabel Kelly

The aim of a preventive vaccine is to exploit the key differences between host responses which lead to a successful outcome (clearance) as opposed to a unsuccessful outcome (persistence).

Many groups have studied patients with acute infection, although this is rarely encountered clinically.

It is clear from such studies that those who go one to clear the virus typically mount –and sustain – broad T cell responses, both CD4 and CD8. These often target multiple epitopes and are maintained long after virus has been cleared from the blood.

Although there is no fixed correlate of protection, this sort of immune response is what we are aiming for in a vaccine – i.e. a broad and robust T cell responses including both CD4+ and CD8+ T cells. Although such a vaccine would not prevent the first stages of infection, emergence of such cells at an early stage could tip the kinetic balance in favour of the host such that viral factors such as escape, exhaustion and regulation – all of which are promoted by high virus loads and sustained replication – do not occur. Such a strategy has been shown to be effective in animal models.

Clinical trials

Currently we are trialling, in collaboration with Okairos, vaccine strategies that induce T cell responses to HCV NS genes using 3 vectors. These are two different adenoviruses, AdCh3 (derived from a Chimpanzee virus) and human Ad6, as well as an Modified Vaccinia Ankara (MVA), all replication deficient.

In June 2011 we completed the first trial of such vectors (HCV001) in healthy volunteers, using both adenoviral vectors in a prime boost regimen. We are now using ChAd3 and MVA vectors in a prime boost regimen in healthy volunteers (HCV003).

At the John Radcliffe Hospital (Oxford) and the Queen Elizabeth Hospital (Birmingham) patients infected with hepatitis C are receiving the same vaccines –again in prime boost regimens (HCV002). We know, from work in our group and others, that a hall- mark of chronic HCV infection is a weak and narrowly focused anti-viral T cell response. The reasons for this are thought to include high viral loads that “exhaust” anti-viral immunity, and infection within the tolerogenic liver environment that primes ineffective anti-viral responses. The vaccines are being given in conjunction with current gold-standard therapy -the idea is to decrease the viral load with conventional therapy before vaccination to give the vaccines the best chance to recover HCV specific T cell immunity.