Understanding how the immune system responds to hepatitis C is crucial in developing a vaccine. An ongoing study by Andrew Lloyd and his team is hoping to shed light on this virus and its weaknesses.
Fiona Wylie (Australian Life Scientist)
04 August, 2010 10:35
This feature appeared in the May/June 2010 issue of Australian Life Scientist. To subscribe to the magazine, go here.
Professor Andrew Lloyd of the University of New South Wales is one of the central figures in the HITS study (Hepatitis C Incidence and Transmission Study) is a long-term prospective cohort study of eligible prison inmates in NSW. Lloyd’s cohort comprises high-risk, uninfected injecting drug users, who are followed at regular intervals longitudinally.
“Sadly we are identifying a significant number becoming infected,” he says. And this is despite significant education on preventative behaviours. “In terms of a hepatitis C vaccine, prisons are, for better or worse, a typical venue that might be targeted as a population in terms of vaccine preparation in the first instance, and ultimately for application of a effective vaccine.”
According to Lloyd, the ideal target population for a candidate hepatitis C vaccine must be well characterised, with well-understood risk behaviours, and a high documented incidence as well as a good follow-up likelihood, so that the effects of the vaccine on incidence are easier to interpret and more significant.
“These criteria are reasonably readily available in our prison population, but not so easy to find within the general population, particularly as injecting drug users, who are the main sufferers of hepatitis C in Australia, tend to be fairly socially chaotic (as a broad statement) outside the prison venue. We recently reported that, sadly, the prison population has an annual incidence of infection of about 30-40 per cent, which is very high.”
The success of hepatitis C vaccine development also requires some knowledge of the protective immunity strategies used by the body against the virus. “What we know already about hepatitis C infection is quite interesting,” says Lloyd.
“For a start, about one in every three people will successfully clear the virus after infection. This is good, because it means that there is something that the host immune response can do to get rid of the virus. The bad news is that most of those people apparently remain susceptible and so can get reinfected.
“Although, it also seems that re-exposure has a better outcome the second time around, meaning that your likelihood of clearing the virus on round two, three, four or five appears better than on the first round. So the evidence suggests that, yes, there probably is such a thing as protective immunity.”
Developing a hepatitis vaccine
The final part of Lloyd’s discussion at the ASM meeting will focus on recent work by the group regarding cellular immunity against hepatitis C infection. As part of the HITS study, Lloyd has been looking at high-risk cohort members who remain uninfected.
“These individuals have been using drugs, sharing needles and doing all the other high-risk behaviours for many years, but have no evidence whatsoever of the virus, by antibody testing and by PCR. And that is really a bit of a surprise,” he says.
“We know that the key element of the immune response that confers successful clearance is cellular immunity – that is, T cells reactive against the virus – and we have found that a significant minority of these high-risk, hard-core, long-standing injectors that were not infected actually have cellular immunity against hepatitis C infection.”
Analyses of T cells within this prison sub-group revealed a population of T cells with the right markers of defence against the virus and which are reactive against the virus when challenged in vitro, suggesting that these individuals have a degree of naturally occurring protective immunity.
“From the vaccine aspect, this means that for some individuals you don’t need to induce de novo primary immunity, but rather to simply boost pre-existing immunity, and the characteristics of that naturally occurring immunity might provide a facsimile of what you might try to generate with a vaccine.”
Current efforts are now focused on better characterising this immunity and in doing so, guiding the strategies for vaccine development and other prevention strategies in both the prison setting and the general community.
The HITS prison study being undertaken under the guidance of Lloyd, together with a more recently established community-based HITS cohort, is providing vital information for the global efforts to develop an effective hepatitis C vaccine.
As Lloyd explains: “It is such an important, time-consuming and challenging task to develop the right vaccine in the research lab, but in the hep C business, it is equally tough to find and manage the right populations to test candidate vaccines.”
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