Published on Monday 23 January 2012 23:44
“An early clinical trial of a hepatitis C vaccine has shown ‘promising’ results,” BBC News has today reported.
This story is based on a clinical trial that tested the dosage and safety of a newly developed vaccine against the hepatitis C virus. Researchers developed a vaccine by inserting small pieces of DNA from a hepatitis C virus into a rare form of the virus that causes the common cold. When faced with a vaccine like this, the body should mount an immune response and ‘remember’ the virus so that it can respond swiftly to any potential infections in the future. The researchers found that cells indicating immunity to the virus were present for a year in 41 healthy people who were vaccinated. This suggests that the immune system was prepared to respond if faced with the virus. None of the people involved with the study experienced significant side effects.
This was an early-stage clinical trial designed to test the safety of the vaccine rather than whether it could prevent infections. Extensive further research will now be needed to determine effectiveness, particularly whether or not it can prevent hepatitis C infections in real-life settings. Given the complexities of testing and development, it is likely to take many years before any such vaccine could enter clinical use.
Where did the story come from?
The study was carried out by researchers from the Universities of Oxford and Birmingham, and from institutions throughout Italy. The research was funded by the European Union, the UK Medical Research Council, the Wellcome Trust, the UK National Institute for Health Research and the US National Institutes of Health.
The study was published in the journal Science Translational Medicine.
The media reported on this study appropriately, with both the BBC and the Daily Mirror emphasising the early nature of the research and the fact that the possibility of a working vaccine is still several years away.
What kind of research was this?
This was a phase I clinical trial that tested the safety and tolerability of a new vaccine intended to prevent infection with the hepatitis C virus. The virus primarily affects the liver, causing inflammation and damage to the organ. It can lead to severe liver scarring (cirrhosis) and liver cancer. There are currently no vaccines available to protect against infection with hepatitis C, and treatments vary in effectiveness depending upon the specific strain of the virus causing the infection.
The Health Protection Agency estimates that more than 200,000 people have the disease in the UK, and that many carry the virus without knowing it. Approximately 20% of people infected with the virus have a natural immunity to it and will clear the virus within the first six months after infection, before the disease is considered to be chronic. Among those who develop chronic hepatitis C, most can clear the infection with the help of drugs, although not all respond to treatment and some remain chronically infected. As a blood-borne virus, it is particularly common among intravenous (IV) drug users.
The development of an effective vaccine would be invaluable, as the World Health Organization estimates that around 130-170 million people around the world have chronic hepatitis C, and therefore could pass the infection on. Certain countries are also reported to have very high rates of hepatitis C, with around 22% of the Egyptian population having a chronic infection.
Phase I clinical trials are conducted in small groups of healthy individuals, and are designed to test the safety and tolerability of new drugs and therapies. They are not designed to test the effectiveness of new treatments, although the results are used to determine the dosing regimen that should be used in future studies. Such small, early studies are required before larger, longer-term research can be conducted to assess the effectiveness of the therapy.
What did the research involve?
The researchers made the vaccine by inserting small pieces of DNA from the hepatitis C virus into a rare form of the virus that causes the common cold. They injected 41 healthy volunteers with the vaccine, and collected data on any side effects, as well as the scale and duration of the immune response. Two rounds of the vaccine were given – an initial priming dose and a subsequent boosting dose four weeks later.
They first conducted ‘dose-escalation’ studies to determine the size of vaccine dose that produced an optimal immune response. The researchers divided the volunteers into groups of four or five people, with each group being given a different dose of the vaccine. They assessed the immune response and tolerability of the vaccine at each of these increasing doses.
The researchers also assessed, in laboratory experiments, whether the immune responses would hold against different strains of the hepatitis C virus, including the strain most commonly affecting European IV drug users (a group that is at highest risk of hepatitis C infection in the UK). To do this they took a blood sample from the study participants, challenged the blood cells with proteins found in different strains of the virus, and analysed the immune response. This was done using laboratory tests. No participants were exposed to these viruses.
What were the basic results?
The researchers found that there were no serious side effects associated with the vaccine. They observed mild side effects that increased at higher doses, but they were short lived.
The researchers determined an optimal dose for the vaccine, and found that the immune response elicited by this dose was similar to that seen in people who have a natural immunity to the hepatitis C virus. They were able to detect this immune response up to a year after vaccination.
They found that the vaccine elicited an immune system response to multiple hepatitis C strains, including the strain that is most common to European IV drug users. The immune response to this strain was, however, approximately only 20% of the response seen to the strain used in the vaccine. Despite this lower response level, this was still higher than the response seen in control subjects not given the vaccine. This indicates that the vaccine did in fact produce some immune response against a common European strain of the virus.
How did the researchers interpret the results?
The researchers say that this study indicates that the vaccine can induce a sustained immune response to the hepatitis C virus, and that further clinical studies into its use as a preventative and therapeutic agent are needed. The next step, they say, is to test it in a setting where exposure to the hepatitis C virus is common, such as in IV drug users, which could help test whether the immunisation is an effective vaccine.
Conclusion
This was a small, early-stage human study into a new vaccine against the hepatitis C virus. While such research is required to determine the safety profile of a new therapy, little information on the effectiveness of the vaccine can be gleaned from the study.
Phase I clinical trials are designed to determine the optimal dose of a new therapy, and to assess the safety and tolerability of treatments. This study shows that the developed vaccine is well tolerated and safe to use, and the preliminary results indicate that the immune response may be similar to that of people with a natural immunity to the virus.
In addition to the small study size and the focus on safety and not effectiveness, there are other practical limitations to the study that should be considered before it is concluded that a preventative vaccine against hepatitis C will be available, even in the next several years:
- Further research is needed to determine whether the vaccine will be effective over a longer period than a year.
- The researchers say that the specific strain of the hepatitis C virus used in the vaccine is common in the US, but that it is not the most common strain in the UK. This may limit how useful any future vaccine is in this country.
- The researchers point out that there are difficulties surrounding the design and execution of future trials, as the virus is common to specific subgroups of people. Future trials will need to be conducted in high-risk groups in whom the predominant virus strain is the same as the strain used to develop the vaccine.
All in all, this was an important initial study into the development of a vaccine against a virus that is difficult to detect and treat. As this was an early-stage study, it will be several years before it could potentially result in an available vaccine.
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