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May 29, 2007
Hepatitis C Vaccine Shows Promise in Chimpanzees
Scientists have developed an experimental vaccine that triggers protective immune responses and helps to control hepatitis C infection in chimpanzees.
Hepatitis C virus infects about 170 million people worldwide and is the leading cause of liver failure in the U.S. But because the virus causes few or no physical symptoms, many people aren't even aware that they are infected. Left untreated, hepatitis C virus often leads to long-term infections that can cause cancer or cirrhosis of the liver. Several research teams are attempting to create vaccines that either block the virus altogether or at least prevent long-term infections from taking hold.
Dr. T. Jake Liang, chief of the liver diseases branch at NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and his colleagues are developing a potential hepatitis C vaccine with virus-like particles that mimic the virus. They contain important viral proteins but no genetic material, so they can't cause infection. Today's widely used vaccines for cervical cancer and hepatitis B are both based on virus-like particles.
The particles produced by Liang and his team consist of 3 structural proteins, including 2 envelope proteins found on the viral surface. In recent years, the scientists have shown that this experimental vaccine can elicit virus-specific immune responses in baboons and genetically altered mice. Moving a step closer to the clinic, the scientists tested the potential vaccine in chimpanzees, the only animal besides humans that is known to become infected with hepatitis C virus.
As reported in the May 15, 2007, issue of the Proceedings of the National Academy of Sciences, the researchers administered 4 doses of the vaccine to 4 chimpanzees over an 8-month period. Three weeks later, the animals were given an infectious dose of hepatitis C virus, a procedure known as a viral challenge. For comparison, 4 non-vaccinated chimpanzees also were injected with the virus, but at a much lower dose.
After the viral challenge, all 4 vaccinated chimpanzees became briefly infected. The vaccine did not trigger production of antibodies to the structural proteins, but within 10 weeks, the cellular immune responses to the hepatitis C virus had climbed significantly, and the virus became essentially undetectable for at least a year. In contrast, 3 of the non-vaccinated animals developed persistent infections with high levels of the hepatitis C virus, and the fourth had an acute infection that eventually cleared.
Human studies have shown that antibodies are not always needed to fight off hepatitis C infection. Ideally, though, a hepatitis C vaccine would trigger both arms of the immune system. Nevertheless, these findings provide proof-of-principle that virus-like particles can produce protective immunity against infection with the hepatitis C virus. Liang and his colleagues say that their virus-like particles can be readily modified — by adding more viral components or making other adjustments that encourage antibody production — to ultimately boost their infection-fighting potential.
— by Vicki Contie