Genetic 'instruction set' for antibodies knocks down hepatitis C in mice

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 reported in the Sept. 17 issue of 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.

Hepatitis C affects roughly 170 million people worldwide and causes chronic liver damage and cancer. The virus is transmitted to humans via contact with contaminated blood during intravenous drug use or medical procedures. 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, explained lead author Alexander Ploss, an assistant professor in Princeton's Department of Molecular Biology. Such antibodies are called "broadly neutralizing" because they deactivate a variety of genetic subtypes. The ones used in the study were discovered by co-author Mansun Law and his team at the Scripps Research Institute in La Jolla, California.

Rather than injecting the actual antibodies - which can be degraded before reaching their targets - the researchers 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, a delivery technique pioneered by co-author David Baltimore and colleagues at the California Institute of Technology.

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.

Hepatitis C infection often has no symptoms. But your doctor may suspect you have it if you have a high level of certain liver enzymes.

Antibody Test

The first test used to check for hepatitis C infection is a blood test for the hepatitis C antibody. Your body makes this antibody when it is infected with the hepatitis C virus. The doctor can send the blood to a lab to be checked, or use a rapid test called OraQuick. The rapid test takes about 20 minutes.