Researchers suggest new approach to hepatitis C vaccine development

Dec. 1, 2014

A triple-punch of antibodies both prevented hepatitis C infection and wiped out the disease after it had established itself in laboratory mice, according to a study led by Princeton University researchers. Instead of delivering the three antibodies directly, the researchers administered a genetic “instruction set” that, once in a cell, developed into antibodies that target the portions of the virus that do not mutate.

Mice treated with the antibody genetic code resisted becoming infected with hepatitis C when they were exposed to the virus, the researchers report in the journal Science Translational Medicine. The researchers also gave the antibodies to mice that already were infected and found that, in many cases, the infection disappeared to levels below detection.

Attempts to develop a hepatitis C vaccine have been hampered by the virus's ability to mutate into numerous subtypes. This genetic diversity is a barrier to developing traditional vaccines, which work by eliciting an immune response against a specific protein or other feature on the surface of the viral particle. These protein targets frequently change when the virus mutates.

To get around this problem, the researchers selected antibodies known to target parts of the virus that tend not to change during mutation. Rather than injecting the actual antibodies—which can be degraded before reaching their targets—they injected the genetic instructions for making the three antibodies. These instructions consist of the antibodies' genetic codes, or DNA, each linked to the DNA for a benign virus called adeno-associated virus (AAV). This virus acts as a ferry that brings the antibody genes into cells. Once inside the cells, the genetic codes were translated by the cell's machinery into hepatitis C antibodies, which were excreted into the bloodstream where they attached to the proteins on the viral surface to inactivate them.

The investigators found that mice injected with the AAV-antibody particles went on to develop high and sustained levels of the antibodies against the virus in their blood, and these antibodies protected them from becoming infected when they were later exposed to the virus. Read the study abstract.

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