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First trial of a new hepatitis C vaccine shows promise

4 January 2012

A new vaccine against the chronic liver disease hepatitis C has shown promising results in a first clinical trial in humans, Oxford University researchers report.

The vaccine, based on a modified cold virus, generated immune responses similar to those seen in the minority of people who are naturally able to clear any infection with the hepatitis C virus.

The findings suggest it might be possible to develop a vaccine that will be broadly effective against hepatitis C and offer lasting protection.

The researchers are hopeful that in time, this work could lead to a vaccine that protects those at risk from the disease or helps in treating those with hepatitis C infections. They caution that many more studies over a number of years would be needed in developing such a vaccine.

‘We’ve found that it’s possible to prime large cellular immune responses against hepatitis C that last for at least a year,’ says Professor Paul Klenerman of the Nuffield Department of Clinical Medicine at Oxford University.

‘The immune responses we’ve seen are exciting and we are beginning the next stage of trials. While we are hopeful, it could be a long road to any vaccine that protects people against hepatitis C,’ he adds.

Hepatitis C is a virus that constantly changes its make-up, like HIV. This makes it a very difficult target for designing a vaccine.

The Oxford researchers, along with colleagues from an Italian biotech company and the University of Birmingham, have used a new approach to stimulate a different arm of the body’s immune system from previous attempts at a vaccine.

Their vaccine is designed to generate a T cell response to the more constant internal parts of the hepatitis C virus, rather than looking to prime an antibody attack on the ever-changing outer coat of the virus.

‘The outside shell of the hepatitis C virus is very variable but the inside of the virus is much more stable. That’s where the engine of the virus is, where we may be able to successfully target many of the crucial pieces of machinery,’ explains Professor Klenerman. ‘But we need T cells and not antibodies to be able to react to the inner components of the virus.

’The study is published in the journal Science Translational Medicine. It was funded by the European Commission along with support from the UK Medical Research Council, the Wellcome Trust, the Oxford Biomedical Research Centre, and the Oxford Martin School at the University of Oxford.

The Oxford University researchers carried out a first clinical trial in humans with the new vaccine.

The phase 1 study was done primarily to gain safety data on the vaccine and determine an appropriate dose and vaccination scheme. It also recorded what kind of immune response was generated. In total, 41 healthy adults participated in the study.

The vaccine appeared safe in this group: there were no significant adverse effects reported. Participants may have experienced some local pain and tenderness at the injection site, or a mild headache.

The researchers found that the vaccine could stimulate a large T cell response against hepatitis C that lasted for at least a year (the length of the study).

The immune response was of a similar type and size to that reported in people who naturally clear the virus from their bodies after infection. Around one in five people are thought to clear the virus spontaneously after infection.The immune response was broad – T cells reacted to a large range of different elements in the hepatitis C virus – and there was some response to other strains of the hepatitis C virus.

The Oxford researchers are now carrying out a trial to see if the vaccine can help treat those already infected with hepatitis C, as well as continuing to develop the vaccine to get better immune responses.

‘T cell responses often become weak in those with chronic hepatitis C infections,’ explains Professor Klenerman. ‘It may be that using a vaccine to boost their immunity could become part of any treatment with other drugs.’

A US team is also looking to carry out a larger trial in at-risk groups to see if the vaccine can offer any protection against infection with hepatitis C.

For more information please contact Professor Paul Klenerman on +44 (0)1865 281885, +44 (0)7769 861085 or paul.klenerman@medawar.ox.ac.uk
Or the University of Oxford press office on +44 (0)1865 280530 or press.office@admin.ox.ac.uk

Notes for editors

  • There is currently no vaccine for hepatitis C. This is because the outside coat of the virus mutates very easily, much more so than HIV, making it a moving target against which to design a vaccine. There are also six different strains of the virus, making it difficult to develop one vaccine that works for all types
  • It is estimated that about 200,000 to 500,000 people are infected with hepatitis C in England and Wales, and the disease is now the leading reason in the West for liver transplants.

    Hepatitis C is caused by a virus transmitted through the blood, with infection typically remaining hidden for many years. Many people do not know they are infected because they do not show any symptoms.

    The course of hepatitis C is unpredictable. In a number of people infection with hepatitis C leads to gradual damage to the liver than can eventually lead to cirrhosis. Some people’s immune responses, however, are sufficient to clear the virus soon after infection, which gives hope that a vaccine might be possible. This is thought to happen in around one in five people.

    Standard treatments for hepatitis C infection are expensive, only clear the infection in around half of people and can have significant side effects. While new drugs have just been licensed, and others are in the pipeline, a vaccine to treat the disease or prevent infection in those at risk would be a great advance.
  • The new hepatitis C vaccine is based on a modified adenovirus developed by research partners in a biotech company in Italy. This work is the subject of another paper in the same issue of the journal Science Translational Medicine.

    Adenoviruses are a family of viruses known as a cause of the common cold and other infections, such as sore throats. Adenoviruses are known to stimulate good T cell immune responses and can be modified so that they don’t replicate and cause an infection, making them a good option for developing vaccines.

    The Italian team were able to use adenoviruses that are rare and are not found circulating in large numbers in the population. This limits the likelihood of people already having an immune response to the adenovirus, which could limit the effectiveness of any vaccine.

    The Oxford-Italian research team introduced a number of elements from the core of the hepatitis C virus into the adenoviruses with the aim of generating a T cell response to hepatitis C.

    This study is the first clinical trial in humans of such an approach to a hepatitis C vaccine.
  • The paper ‘Novel adenovirus-based vaccines induce broad and sustained T cell responses to HCV in man’ by Eleanor Barnes and colleagues is to be published in the journal Science Translational Medicine.
  • The study was funded by the European Commission and also the UK Medical Research Council, the Wellcome Trust, the Oxford Biomedical Research Centre, and the Oxford Martin School at the University of Oxford.
  • The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk
  • For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk
  •  The NIHR Biomedical Research Centre, Oxford is a partnership between the research expertise of the Oxford Radcliffe Hospitals NHS Trust and the University of Oxford. Its main aim is to enable clinical research for patient benefit and foster innovation to improve healthcare. It is funded by the National Institute for Health Research (NIHR). The NIHR provides the NHS with the support and infrastructure it needs to conduct first-class research funded by the Government and its partners alongside high-quality patient care, education and training. Its aim is to support outstanding individuals (both leaders and collaborators), working in world class facilities (both NHS and university), and conducting leading edge research focused on the needs of patients.
  • Oxford University’s Medical Sciences Division is recognized internationally for its outstanding research and teaching, attracting the brightest minds from all over the world.

    It is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students, and brings in around two-thirds of Oxford University’s external research income. Listed by itself, that would make it the fifth largest university in the UK in terms of research grants and contracts.

    Oxford is home to the UK’s top-ranked medical school, and partnerships with the local NHS Trusts enable patients to benefit from the close links between medical research and healthcare delivery.

    14 winners of the Nobel Prize for Physiology or Medicine worked or were educated at Oxford, and the division is home to 29 Fellows of the Royal Society and 68 Fellows of the Academy of Medical Sciences.

    The development of penicillin at Oxford ushered in the modern age of antibiotics, and the confirmation of the link between smoking and cancer has prevented many millions of deaths. Oxford continues to be at the forefront of medical research, whether it’s the genetic and molecular basis of disease, the latest advances in neuroscience, or clinical studies in cancer, diabetes, heart disease and stroke. Oxford has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic.

    A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.