Discovery of Hepatitis C Blocking Antibodies Suggests Strategies for Improving Treatment and Prevention
A discovery made by Food and Drug Administration scientists in the Center for Biologics Evaluation and Research (CBER) and their colleagues at the National Institutes of Health could lead to a significant reduction of illness and medical costs from hepatitis C virus (HCV) infections.
The CBER scientists identified "blocking" antibodies that interfere with antibodies that would otherwise neutralize HCV. This discovery suggests that eliminating blocking antibodies would permit neutralizing antibodies to clear the body of HCV.
About 170 million people worldwide are infected with HCV, including 4 million in the US. More than 70% of individuals infected with HCV fail to clear the virus from their body. About 20% of these chronically infected individuals subsequently develop cirrhosis, which can lead to liver cancer. HCV-associated cirrhosis is the leading indication for liver transplantation in the US.
The results of the study are important because one of the obstacles to developing an effective HCV vaccine has been the lack of understanding how HCV infection persists despite the presence of neutralizing antibodies. Based on this new insight, CBER scientists are now trying to develop an effective vaccine by mutating the targets on HCV that trigger production of blocking antibodies so these antibodies are no longer produced.
In addition, the target of the blocking antibody is variable, that is, it mutates readily. But the target of the neutralizing antibody is relatively constant among different subtypes of HCV. Therefore, eliminating blocking antibodies would enable neutralizing antibodies originally made against one subtype of HCV to bind a broad array of subtypes of the virus, enhancing its effectiveness as a therapy.
The CBER/NIH discovery could also lead to improved treatment of patients already infected with HCV. The current treatment using preparations of antibodies manufactured from anti-HCV-positive plasma (HCIGIV) fails to reduce HCV levels or prevent a repeat infection after liver transplantation. CBER researchers are evaluating whether depleting interfering antibodies from HCIGIV would enhance its ability to neutralize HCV and prevent the virus from infecting cells.
"Depletion of interfering antibodies in chronic hepatitis C patients and vaccinated chimpanzees reveals broad cross-genotype neutralizing activity"
Proceedings of the National Academy of Sciences USA