Article

Why Hepatitis C Eludes Traditional Vaccine Targets

Hepatitis C mutations help the virus dodge vaccines.

infectious disease, hepatitis C, HCV, hepatology, vaccination, vaccine

Researchers have long been facing barriers to developing a hepatitis C vaccine. The virus, which infects between 2.7 and 3.9 million people in the United States, mutates and outruns immune system responses.

New research from Johns Hopkins Medicine found that a novel tool has identified a biological mechanism that helps hepatitis C dodge the immune system and vaccines.

Using a large library of naturally occurring hepatitis C virus strains, the researchers sorted through viral mutations to see which ones assist the virus in evading immune system responses. They determined that mutations that happen outside of the viral sites usually targeted by antibody responses are key in resistance.

“We think those mutations could account for the difficulty of making an effective vaccine,” Justin Bailey, MD, PhD, (picture) assistant professor of medicine at the Johns Hopkins University School of Medicine, said in a news release. “These are the mutations we believe may allow the viruses to avoid being blocked by antibodies altogether.”

From there, the team gathered 113 hepatitis C strains from 27 patients treated at The Johns Hopkins Hospital. The strains were tested against HC33.4 and AR4A, two potent antibodies commonly used in hepatitis C vaccine trials.

The researchers explained that natural hepatitis C viruses don’t do well in the lab setting, so they created pseudo-viruses with the use of HIV capsules, since that virus easily grows in the lab. The surface proteins from the hepatitis C virus strains were placed on the pseudo-viruses to infect human cells in tissue cultures.

The virus strains were equally separated to either receive HC33.4 treatment, AR4A treatment, or no treatment. HC33.4 and AR4A neutralized 88% and 85.8% of the virus, respectively. First author Ramy El-Diwany, a student at the Johns Hopkins University School of Medicine, explained that they observed a lot of naturally occurring resistance.

The antibody treatments had greater impact on some hepatitis C strains than others, and some strains weren’t affected much at all. So, using a genetic sequences program, the team looked at the virus genomes. Results showed that there was a wide range of resistance to both treatments, but even so, binding sites remained similar. More specifically, the HC33.4 only had one binding site mutation while the AR4A binding site was the same for all hepatitis C strains.

“If you think of it like a race, the antibody is trying to bind to the virus before it can enter the cell,” Baily continued. “We think this mutation may allow the virus to get into the cell before it even encounters the immune system.”

Further investigation revealed that binding site mutations weren’t connected to resistance, but surface protein mutations located away from the binding site showed high infection level even with treatment.

Although hepatitis C treatments can cure the virus, drugs can’t reduce the risk of future infection. Since many people with the virus aren’t aware they’re infected, it will take a vaccine to eliminate hepatitis C infection, El-Diwany said.

The study, “Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1,” was published in PLOS Pathogens. The news release and headshot were provided by Johns Hopkins Medicine.

Related Coverage:

Cirrhosis Doesn’t Lead to Liver Cancer as Often as Thought

Hepatitis C Genotype Makes a Difference in Liver Disease, Study Shows

How Long Does Acute Hepatitis C Remain in the Pre-Seroconversion Window?

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