Recently, scientists from Princeton University "ordered" mice to produce three kinds of antibodies, successfully preventing hepatitis C virus infection. They also used this method to clear the virus from the body of the infected mice.
Previously, people's attempts to develop a hepatitis C vaccine have been unsuccessful. Because the hepatitis C virus has a strong ability to mutate, the viral regions of traditional vaccine targets often change. For this reason, this study selected antibodies to the conservative part of the target virus, said Alexander Ploss, an assistant professor at Princeton University who led the study. These antibodies are also called broad-spectrum neutralizing antibodies.
If antibodies are injected directly into mice, they may be degraded before they reach their destination. So the researchers integrated genetic instructions (DNA encoding antibodies) into the non-toxic adeno-associated virus AAV vector. This technique of delivering antibody genes into cells is called VIP (vectored immunoprophylaxis) and was developed by Nobel Laureate Professor David Baltimore of Caltech, who is also one of the co-authors of this research.
After the above coding sequence enters the cell, it can be translated into hepatitis C antibody and secreted into the blood. These antibodies can attack hepatitis C there and inactivate the virus.
Researchers found that after mice were injected with AAV-antibody particles, there were persistently high levels of antiviral proteins in the blood, and these antibodies could protect the mice from virus infection. "A single intramuscular injection can fill the blood with a lot of antibodies for several months," Ploss said.
Researchers also injected AAV-antibody particles into mice that had been infected with hepatitis C. "We are not sure about the results, because these antibodies can only neutralize the virus outside the cell, and virus replication occurs inside the cell." Ploss said. "Surprisingly, the virus levels in the blood of the mice dropped within a few weeks, and the virus levels in many mice even fell below the detection limit."
Hepatitis C is widespread in many regions of the world, so new strategies to prevent hepatitis C are urgently needed. Eight out of ten people with hepatitis C infection will develop chronic infections, leading to progressive liver disease and scarring. The disease of most infected people can lie latent for more than ten years. A new drug that can cure hepatitis C came out in 2013, but its price is very high and it is difficult to be widely used (especially in developing countries).
Hepatitis C virus discoverer Michael Houghton believes that this research is expected to help people develop inexpensive and effective hepatitis C treatment drugs.
Ploss pointed out that broad-spectrum neutralizing antibodies can eliminate established hepatitis C infection, which may reveal the mechanism by which hepatitis C virus maintains chronic infection in the human body. "From the current results, for the virus to maintain a continuous infection, it needs to continuously infect new cells instead of relying on previously infected cells," he said. "Our antibodies may have destroyed this chain of infection. This shows that long-term treatment with broad-spectrum neutralizing antibodies can play an effective therapeutic role."