Doctors can quiet the hepatitis B virus, but they cannot make it leave. A hepatitis B functional cure – lasting control without daily drugs – has stayed out of reach.
Standard daily pills push viral levels near zero. Stop them, and the virus rebounds fast, as if the treatment never happened.
One injection given to 27 patients with chronic infection broke that pattern. The immune response it woke up did not fade with time. More than two years later, it was still growing.
A different approach
The idea is simple to state and hard to pull off. Rather than adding another drug to suppress the virus, it pushes the patient’s own immune system back into the fight.
Professor Edward Gane of the University of Auckland presented the findings in Barcelona. The treatment, VRON-0200, went to 27 adults whose infection was controlled by antiviral pills.
Everyone got one shot in the arm, and some a later booster. Nobody stopped their medication. The question was whether a single injection could stir a response the daily pills never do.
Waking tired defenses
In a chronic hepatitis B infection, the immune cells that should hunt infected liver cells wear out. That breakdown, mapped in an earlier study, helps explain why the virus digs in.
The shot carries viral components using two harmless carrier viruses from chimpanzees. They give the immune system a clear look at its target, waking the exhausted cells that should hunt it.
It also carries a component meant to loosen the brakes the body keeps on its defenses. The treatment never targets the surface protein doctors track, yet that protein began dropping anyway.
What the trial showed
A year after the single dose, most patients showed something doctors rarely see in so stubborn an infection. In 23 of 27, levels of that surface protein held steady or kept falling.
About half saw their levels fall by more than 50 percent. A few dropped much further – a tenfold reduction or more. That kind of change usually takes far more than one shot.
None of this came with the serious side effects that can sink an experimental treatment. The trial logged no dangerous reactions and no dropouts, and liver tests stayed normal throughout.
Declines that kept going
The surprise came later. When researchers rechecked a dozen patients, some more than two years past that first shot, the protein had not crept back. In 11 of 12, it was still falling.
Two of these patients cleared the surface protein from their blood entirely, the result that defines a functional cure.
The longest follow-up reached 846 days, well past the point where an immune response usually fades. Instead, it appeared to keep growing.
It was something no one had shown before. Earlier attempts to rouse the immune system faded once the push stopped. Here, one dose set off a response that carried on by itself.
Why rebound happens
Today’s pills work well, squeezing the virus down to almost nothing. The catch is that they leave the immune system weak. Stop taking them, and the virus usually returns within weeks.
That bounce-back is the main obstacle to a cure. One paper following patients who quit treatment found the virus returning in one in five. The goal is for the body to keep the virus suppressed on its own.
Against that backdrop, declines holding for two years without a single rebound stand out.
These patients stayed on their pills, so the follow-up cannot prove the shot alone keeps the virus down. Still, it shows an immune response that strengthened rather than stalled.
Spark and fan
Behind the treatment is a two-step plan the researchers call spark and fan. One shot lights the spark, and later antivirals fan it into something strong enough to clear the virus.
Researchers have chased therapeutic shots for hepatitis B for years, and a long review shows how many fell short. The durability seen here sets this attempt apart.
A larger trial is now underway, testing whether patients can stop their pills entirely and keep the virus down. It will also enroll people with higher protein levels, a tougher group.
Toward a functional cure
For the first time, a single shot has restored a lasting immune response against chronic hepatitis B, holding for over two years without a rebound. Nothing like it had been shown before.
That opens a door the field has wanted for years. Instead of a lifetime of daily pills, some patients might take a short course, then lean on their restored defenses to keep the virus quiet.
Almost 260 million people live with chronic hepatitis B, and it kills over a million people each year. A one-shot treatment switching those defenses back on would reach far beyond this trial of 27.
The study is published in the journal The Lancet Microbe.
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