Key ingredient for a universal flu vaccine, found in llama blood

Llamas make an array of immune system antibodies so tiny they can fit into crevices on the surface of an invading virus.That feat could one day protect humans from entire families of flu viruses that bedevil scientists with their unpredictable and shape-shifting ways


A universal flu vaccine could finally end this inefficient guessing game. According to the National Institutes of Health, such a vaccine should be 75% effective, protect against group I and group II influenza A viruses (the most common to infect humans), last for at least one year, and be suitable for all age groups.

All, potentially, with a once-a-year nasal spray up the nose.

In a study in Friday’s edition of the journal Science, a team from the Scripps Research Institute in La Jolla and their international colleagues have taken a major step toward the long-sought goal of developing a universal vaccine against influenza.

When they tested their intranasal formulation in mice, it quickly conferred complete protection against a raft of human flu strains adapted to mice. Those include A viruses, such as the H1N1 “swine flu” that touched off a global pandemic in 2009, and B viruses, which occur only in humans.

Against H1N1, a dose of the experimental vaccine was shown to protect for at least 35 days — a span of time equivalent to more than a single flu season for humans.

Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, offered a full-throated appreciation for the new study, which received funding from the National Institutes of Health.

“From a scientific and technical standpoint, this is really a very elegant study — the highest quality of science,” Fauci said. He praised it for demonstrating that in order to protect people from pathogens that can change or emerge unpredictably, scientists must construct vaccines that can knock down an array of viruses, even in people whose immune systems are fragile or compromised.

To fight it, the research team borrowed new techniques from immunology, microbiology, nanotechnology and genetic engineering labs around the world.

First, they vaccinated llamas against a number of A and B strains of influenza. Then they took blood samples to collect the antibodies the llamas produced in response.

Among them were four uniquely small antibodies that showed an ability to destroy many different strains of influenza. In a nod to their size and function, they called their creations ‘nanobodies.’

Influenza is a viral scourge that kills as many as 650,000 people each year, according to the World Health Organization.

Antibodies are weapons of the immune system and they bind to the proteins that stick out from the surface of a virus.

Human antibodies tend to attack the tips of those proteins, but that’s the part influenza mutates most readily.

Llama antibodies use their size advantage to wriggle a little bit deeper and attack the parts that flu cannot change.

The team at the Scripps Institute in California infected llamas with multiple types of flu to provoke an immune response.

They then scoured llama blood for the most potent antibodies that could attack a wide range of flu strains.

They picked four, and then set about building their own synthetic antibody that used elements from each.

It was tested on mice, which were given deadly doses of influenza.

Scripps immunologist and Prof Ian Wilson, one of the researchers, said, “It’s very effective, there were 60 different viruses that were used in the challenge and only one wasn’t neutralised and that’s a virus that doesn’t infect humans.

“The goal here is to provide something that would work from season to season, and also protect you from possible pandemics should they emerge.”

The work, published in the journal Science, is very early stage research and the team want to do more tests before starting human trials.

The researchers tried two approaches in give the animals the antibody.

The first was to inject them with the antibodies, and the second was a type of gene therapy.

The genetic instructions for making the antibody were packaged up inside a harmless virus, which was then used to infect the noses of mice.

The cells in the linings of the nose then started making the flu-killing antibody.

An additional advantage of this approach is that it could work in the elderly.

The older you are the worse your immune system gets, and the less effective the seasonal flu vaccine becomes.

But the llama-inspired approach does not need to train the immune system.

But the researchers still faced a key hurdle: getting the human immune system to make such a super-protein even when it’s weighed down by age, stress and disease.

They devised a way to work around humans’ unreliable response to vaccines, building a gene that encoded the production plans for their powerhouse protein. To ferry that gene into a host organism, they enlisted a harmless virus used by labs working on gene therapy.

By splicing their designer gene into this viral delivery device, the scientists not only found a way to get their antibody package into a host, they were delivering the manufacturing machinery to produce it.

This “passive transfer” of antibodies gives this vaccine candidate the potential to be equally effective in everyone, Fauci said.

The next step is to conduct further tests in animals and clinical trials in humans, and that “will take years,” he said. “But if fully successful — a majestic leap right now – it could essentially eliminate the need from season to season” to divine which of countless possible flu viruses will rear up, and to then build a yearly flu vaccine that neatly fits the bill.

Source: Los Angeles Times