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By studying individuals who spontaneously recover from hepatitis C, researchers have opened the way to a possible vaccine against this infection which affects 70 million people worldwide.
Hepatitis C: why do some patients eliminate the virus naturally?
An estimated quarter of people infected with the hepatitis C virus recover on their own without treatment, while the remaining three-quarters develop chronic infections that can last for years. This blood-borne disease can cause liver cirrhosis, liver failure and liver cancer.
Direct-acting antivirals developed around ten years ago are very effective (98%). However, the number of hepatitis C cases continues to increase because early infections are difficult to detect, access to treatment is limited, and reinfections are possible after treatment. Hence the interest in having a vaccine.
Antibodies that attack from three sides at once
Viruses that evolve very quickly, such as SARS-CoV-2, influenza and hepatitis C, exhibit extraordinary genetic diversity with multiple strains. Fighting these types of infections requires special antibodies (blood proteins that recognize pathogens and neutralize them) called broad-spectrum neutralizing antibodies (bNAbs), which can neutralize various viral variants.
Members of Flyak’s lab used X-ray crystallography to better understand what distinguishes people who recover spontaneously from those who are affected by chronic forms.
According to the researchers, bNAbs from people chronically infected with the hepatitis C virus use a single antibody gene to encode a variable part of the antibody molecule, the front layer of the so-called E2 protein. Result: the immune system of chronically infected people failed to eliminate the virus.
In a person who spontaneously cleared three separate infections, bNAbs revealed important distinctions. First, these bNAbs were genetically diverse, meaning that they are encoded by a variety of variable genes, not just one segment of the gene. Second, this individual’s bNAbs targeted three different regions of the virus’s E2 protein.
Towards more effective vaccine candidates against hepatitis C
The data suggest that a vaccine against the hepatitis C virus should be able to induce the stimulation of bNAbs capable of targeting three regions of the E2 protein rather than just one. “Our study gives us insight into how certain individuals clear a highly variable infection, and we believe this information can inform vaccine development“, said Professor Andrew Flyak, professor of microbiology and co-author of the study.
Next steps: The team will collaborate with a larger international group to review several vaccine candidates in animals and potentially identify which ones to move into human clinical trials.