Researchers have not been able to develop a vaccine for hepatitis C, which causes 700,000 deaths around the world annually, and now, a new study shows why developing a vaccine for the virus has been so difficult.
According to the World Health Organization (WHO), as many as 150 million people globally— more than 2% of the world’s population– live with chronic hepatitis C infections. Developing a vaccine to prevent this deadly virus has proven difficult and new research now explains why.
The hepatitis C virus is a contagious blood-borne disease that leads to inflammation of the liver. A mild or acute infection can last only a few weeks, but it can lead to a more severe and chronic lifelong form of liver disease. According to the Centers for Disease Control and Prevention (CDC), 75% to 85% of people with a acute hepatitis C will go on to develop a chronic infection, and between 2.7 million and 3.9 million people in the United States have chronic hepatitis C. The virus is most commonly spread through the sharing of needles or syringes used for drug injection, though it can also be passed from an infected mother to her baby, through sexual contact, or by sharing personal items such as razors. As the infection progresses, it turns into chronic liver disease, which can then lead to cirrhosis. One to five people out of 100 infected with hepatitis C will die from cirrhosis or liver cancer.
While as many as 25% of those who develop an acute hepatitis C infection will recover without treatment, according to WHO, approximately 700,000 people worldwide die from hepatitis C-related liver disease annually. New and more effective antiviral drugs can cure a Hepatitis C infection in about 12 weeks when infection does not go away on its own, but these drugs are particularly expensive in underdeveloped countries where hepatitis C is prevalent. Public health experts looking for a better way to prevent the spread of the virus have been hopeful for the development of a hepatitis C vaccine, but a new study by researchers at the Scripps Research Institute, recently published in the Proceedings of the National Academy of Sciences, sought to find out why creating such a vaccine for the virus has proven so difficult.
For some time, medical researchers have attempted to develop a hepatitis C vaccine using the viral protein E2, a host receptor binding protein, as the active component to induce an immune response and create protective antibodies, but with no luck. The receptor-binding site on E2 is a key component that allows hepatitis C to infect hosts, and the antibodies that best fight a broad range of the virus strains target this site. While there are at least 67 subtypes of hepatitis C and the virus has high mutation rates, the amino acid sequence of E2 is very similar between strains. In this study, researchers created a lab-made version of E2 and found that the part of the protein meant to make the vaccine active was much more flexible than they realized. Due to the fact that E2 presents in a wide variety of shapes to the immune system, it brings out a wide variety of antibodies, and thus, it is unable to target the viral infection. “Because of that flexibility, using this particular protein in HCV vaccines may not be the best way to go,” said co-senior author Mansun Law, PhD, in a press release.
These findings offer a new direction for hepatitis C vaccine development, according to the study’s authors. “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, D.Sc.