Why Isn't There a Hepatitis C Virus Vaccine Yet?

Vaccine candidates for hepatitis C virus have been notoriously unsuccessful in preventing the infection.

Researchers recently discovered why creating a vaccine against hepatitis C virus (HCV) has been unsuccessful thus far.

Although hepatitis C virus is curable with antiviral drugs, the treatments are very costly, and insurance companies have been hesitant to cover the cost of the drugs for patients without late stage disease.

By using multiple techniques to map molecular structures, a lab-made version of a viral protein was able to be examined. This protein, E2, has been used in investigational HCV vaccines to prompt an immune system to the virus.

Previously, the researchers mapped the atomic structure of E2, including where it binds to liver cells. Since this receptor is critical for the virus, the amino acid structure is the same in each strain.

The receptor binding site is also accessible to antibodies, and many are able to neutralize HCV strains by doing so, according to the study. These factors make it an ideal target for creating a vaccination.

However, vaccine candidates mimicking E2 elicit antibodies against the binding site, but they have not been able to prevent the infection. The researchers in the study looked at the receptor binding site of recombinant E2, which is isolated from the rest of the virus, and makes it an excellent candidate for a vaccine.

They also found that recombinant E2 was extremely stable, and has a high melting point of 85°C, likely from strong disulfide bonds. However, within the protein, the receptor binding site is flexible, and able to take on a variety of shapes.

These findings suggest that using this protein may not be the best option for creating a vaccine.

“We may want to engineer a version that is less flexible to get a better neutralizing response to the key target site and not so many off-target responses,” said co-senior author Ian A. Wilson.

Previous studies have found that the HCV receptor binding site can adopt various conformations when bound by virus-neutralizing antibodies. A vaccination that calls for antibodies against these key conformations would provide adequate protection against the virus.

The most recent findings suggest that recombinant E2 creates too many binding-site conformations, and creates antibodies that do not stop hepatitis C.

An effective vaccination against HCV would prevent the liver damage that eventually causes cancer. By preventing the disease, many patients would be spared the costs and health effects associated with the disease.

The vaccination could also prevent billions of dollars of spending on hospital stays, medical treatments, cancer care, and medications.

Researchers plan to conduct follow-up studies to study E2 and its receptor binding site as it occurs on the virus. They are also planning to create a new type of E2 or a different protein that has a stable receptor binding sight that will elicit the effective virus-neutralizing antibodies, the study concluded.