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,” said Professor Paul Klenerman of the Nuffield Department of Clinical Medicine at Oxford University. He added: ‘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.”
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 NIHR Biomedical Research Centre, Oxford 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