Global Health Press
Scientists move closer to long-lasting flu vaccine

Scientists move closer to long-lasting flu vaccine

As this year’s flu season gathers steam, doctors and pharmacists have a fresh stock of vaccines to offer their patients. The vaccines usually provide strong protection against the virus, but only for a while. Vaccines for other diseases typically work for years or decades. With the flu, though, next fall it will be time to get another dose.

“In the history of vaccinology, it’s the only one we update year to year,” said Gary Nabel, director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases.

That has been the case ever since the flu vaccine was introduced in the 1950s. But a flurry of recent studies on the virus has brought some hope for a change. Nabel and other flu experts foresee a time when seasonal flu shots are a thing of the past, replaced by long-lasting vaccines.

“That’s the goal: two shots when you’re young, and then boosters later in life. That’s where we’d like to go,” Nabel said. He predicted that scientists would reach that goal before long — “in our lifetime, for sure, unless you’re 90 years old,” he said.

Vaccines work by enhancing the protection the immune system already provides. In the battle against the flu, two sets of immune cells do most of the work.

One set, called B cells, makes antibodies that can latch onto free-floating viruses. Burdened by these antibodies, the viruses cannot enter cells.

Once flu viruses get into cells, the body resorts to a second line of defense. Infected cells

gather some of the virus proteins and stick them on their surface. Immune cells known as T cells crawl past, and if their receptors latch onto the virus proteins, they recognize that the cell is infected; the T cells then release molecules that rip open the cells and kill them.

This defense mechanism works fairly well, allowing many people to fight off the virus without ever feeling sick. But it also has a built-in flaw: The immune system has to encounter a particular kind of flu virus to develop an effective response against it.

It takes time for B cells to develop tight-fitting antibodies. T cells also need time to adjust their biochemistry to make receptors that can lock quickly onto a particular flu protein. While the immune system educates itself, an unfamiliar flu virus can explode into full-blown disease.

Today’s flu vaccines protect people from the virus by letting them make antibodies in advance. The vaccine contains fragments from the tip of a protein on the surface of the virus, called hemagglutinin. B cells that encounter the vaccine fragments learn how to make antibodies against them. When vaccinated people become infected, the B cells can quickly unleash their antibodies against the viruses.

Unfortunately, a traditional flu vaccine can protect against only flu viruses with a matching hemagglutinin protein. If a virus evolves a different shape, the antibodies cannot latch on, and it escapes destruction.

Influenza’s relentless evolution forces scientists to reconfigure the vaccine every year. A few months before flu season, they have to guess which strains will be dominant. Vaccine producers then combine protein fragments from those strains to create a new vaccine.

Experts have long wondered whether they could escape this evolutionary cycle with a vaccine that could work against any type of influenza. This universal flu vaccine would have to attack a part of the virus that changes little every year.

Sarah Gilbert and her colleagues at Oxford are trying to build a T cell-based vaccine that could find such a target. When T cells learn to recognize proteins from one kind of virus, the scientists have found, they can attack many other kinds. It appears that the flu proteins that infected cells select to put on display evolve very little.

The scientists are testing a vaccine that prepares T cells to mount a strong attack against flu viruses. They engineered a virus that can infect cells but cannot replicate. As a result, infected cells put proteins on display, but people who receive the vaccine do not get sick.

In a clinical trial reported this summer, the scientists found that people who received the vaccine developed a strong response from their T cells. “We can bring them up to much higher levels with a single injection,” said Gilbert, the lead author of the study.

Once the scientists had vaccinated 11 subjects, they exposed them to the flu. Meanwhile, they also exposed 11 unvaccinated volunteers. Two vaccinated people became ill, while five unvaccinated ones did.

While the Oxford researchers focus on T cell vaccines, others are developing vaccines that can generate antibodies that are effective against many flu viruses — or perhaps all of them.

Source: Pioneer Press