Burnet Institute researchers have re-engineered the major protein of hepatitis C virus (HCV) to expose the virus more effectively to attack by the human immune system, an important step towards the development of an urgently needed preventive vaccine for HCV.
An estimated 700,000 people die each year from HCV-related liver diseases, of the more than 120 million people globally who are infected, according to the World Health Organization (WHO).
The research, led by Associate Professor Heidi Drummer and published in the journal Hepatology, demonstrates how to overcome HCV’s ability to trick the immune system into producing antibodies that hinder an effective immune response.
“What we’ve done is to redirect the immune response to the parts of the virus that you want the immune system to see, and those are the parts that generate broadly cross-reactive antibodies effective against all seven circulating genotypes of virus,” Associate Professor Drummer said.
“We’re redirecting the focus of the immune response away from regions of the virus that generate antibodies that are not only ineffective, but which block the effectiveness of the desirable antibodies.
“It’s the first time this has been demonstrated in HCV that you can actually re-engineer the surface protein to generate a profoundly different immune response that is now cross-reactive and blocks the virus from entering cells.
“That gives us a lead that we can work with to produce a vaccine candidate that’s going to be amenable for a clinical trial.”
Burnet Deputy Director (Programs), Professor Margaret Hellard said a preventive vaccine is urgently needed, particularly in the developing world, as part of a suite of measures to eliminate HCV.
While new direct acting antiviral (DAA) drugs have proved highly effective in curing HCV, they can’t prevent reinfection and are of no benefit to the estimated 50 million people with undiagnosed HCV infections who play a key role in the spread of the disease.
“Prevention is better than cure, so if we can stop people ever getting hep C or being re-infected and ever needing DAAs, that will be a huge saving to the health budget, or private insurance in other countries,” Professor Hellard said.
“It’s a key piece of the elimination puzzle. We really need vaccines, treatment, harm reduction, education, community engagement and diagnosis to work together in a package to reach the WHO elimination targets.”
Associate Professor Drummer said a vaccine would ideally be introduced into existing regimens, for example, as part of a hepatitis A, B, and C vaccine combination in infancy, or administered in combination with the human papilloma virus in adolescence.