December 10, 2022

Protein Analysis Can lead to Hepatitis C Vaccine

A hepatitis C vaccine is one step closer because of the efforts of scientists in the Scripps Research Institute (TSRI), who’ve were able to discover unexpected structural features of a protein utilized by herpes to infect liver cells.

The study authors, whose work appears in Friday’s edition from the journal Science, state any successful hepatitis C vaccine would most likely target this protein, which is known as E2 envelope glycoprotein. Rare antibodies able to binding E2 in ways that can neutralize an enormous variety of different viral strains happen to be isolated in patients by scientists, they added.

“We’re excited with this development,” senior author Dr. Ian A. Wilson, the Hansen Professor of Structural Biology at TSRI, said in a statement. He added it took him and his TSRI colleagues Dr. Mansun Law and Dr. Andrew B. Ward six years of “painstaking work” to complete a higher resolution structure from the protein. They now intend to create vaccines that can mimic the structural details of those binding sites.

According to the Institute, the worldwide spread of hepatitis C has resulted in a desperate need for a highly effective vaccine from the virus. The pathogen, which was once geographically isolated, has found its way throughout the world, primarily because of blood transfusions, the use of unsterilized medical equipment and the re-use of hypodermic needles. While hospitals have screened for that virus for about two decades, you will find believed to be up to 200 million people worldwide have contracted hepatitis C, including over three million in the US alone.

“HCV could spread so widely because it typically causes few or no symptoms if this infects someone. Oftentimes it establishes a long-term infection of the liver, damaging it slowly for decades C until liver cirrhosis and/or cancer develop,” TSRI explained. The study was funded in part by the National Institutes of Health and the Skaggs Institute of Chemical Biology.

The disease, which according to Law is a “silent killer,” is typically fatal unless someone undergoes a costly and high-risk liver transplantation procedure. Some antiviral medications can treat as well as cure chronic hepatitis C infection, but the most effective ones are incredibly expensive, and frequently those people who are infected don’t realize they have the virus and require medical attention. A vaccine could prevent new infections, ending the pandemic.

“It could be provided to people when they’re young and healthy, and they’d never have to worry about developing HCV-related liver diseases,” Ward said. However, unlike HIV along with other viruses, hepatitis C utilizes a number of different effective countermeasures to evade an immune system, including rapidly-mutating regions on the E2 protein which makes sure antibodies that are effective against one strain are not ineffective against others.

The TSRI researchers attempted to analyze the high-resolution atomic structure of the virus to be able to help overcome these countermeasures. However, according to the study authors, that’s been a difficult task to try, let alone complete. It took a large number of experiments to obtain the proper way to modify E2, which makes it so the protein aggregates less readily while making sure that its antibody-binding sites are maintained. Ward named it “a Herculean effort” because hepatitis C is “one of the most difficult and unstable viral envelope proteins around.”

“In the end, the team succeeded, using a slightly altered form of E2 C the E2 core C with some of its glycans (sugar molecules) and outer variable and stalk segments removed,” the Institute said. “The scientists were then able to have the high-resolution structure of the protein although it was bound to a known broadly neutralizing antibody developed at TSRI. The scientists then accompanied by imaging a far more complete version of E2 using electron microscopy to extend the structural model.”