New research may assist in HCV vaccine development

Better understanding of the structure of a hepatitis C surface protein may assist in vaccine development.

New research may assist in HCV vaccine development
New research may assist in HCV vaccine development

New findings suggest researchers may have identified the structure of a hepatitis C surface protein — which may assist in the development of a vaccine against the disease, according to new findings published in Nature.

About 160 million people worldwide have HCV, a disease that often leads to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Yet, no vaccine is currently available and therapies are effective against some, but not all, genotypes, according to background information provided in the study.

"Viruses are smart and it is a constant battle to keep them out,” Joseph Marcotrigiano, PhD, associate professor of chemistry and chemical biology at Rutgers University, said in a press release. “That's why the development of a vaccine is so important. It's always better to prevent infection through an effective vaccine then to treat after a chronic infection has been established.”

HCV consists of two surface glycoproteins — E1 and E2. The E2 glycoprotein serves as a target for neutralizing antibodies by binding to the host cell through interactions with scavenger receptor class B type I and CD81, according to the study.

The E2 core has a compact, globular domain structure, consisting mostly of β-strands and random coil with two small α-helices. These β-strands consist of two, upright sheets held together by a hydrophobic core and disulphide bonds. One sheet has an IgG-like fold most often identified in viral and cellular proteins. Conversely, the second sheet represents a novel fold.

Marcotrigiano and colleagues found that the full-length E2 ectodomain has a similar globular architecture and does not undergo significant conformational rearrangements on exposure to low pH.

“Thus, the IgG-like fold is the only feature that E2 shares with class II membrane fusion proteins,” the researchers wrote. “These results provide unprecedented insights into HCV entry and will assist in developing an HCV vaccine and new inhibitors.”

Developing a vaccine against hepatitis C would not only prevent people from acquiring the disease, according to Marcotrigiano, but would also be the most cost-conscious health intervention.

References

  1. Khan AG et al. Nature. 2014; doi:10.1038/nature13117.

Disclosure: See study for full list of disclosures.

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