Gene therapy that turns cells in the nose into factories that crank out super
antibodies against the flu protected mice and ferrets against lethal doses of
several pandemic strains of the virus.
If the approach works in humans, it could offer several important advantages
over flu vaccines, said study author Dr James Wilson, a professor of pathology
and laboratory medicine at the University of Pennsylvania, in Philadelphia.
Because the therapy can be made ahead of time and fights many different
strains, it might give doctors a faster way to thwart flu pandemics.
Race against time
Currently, doctors race to identify dangerous new types of flu. They then
have to develop a vaccine that targets the new strain. The vaccine is then grown
in chicken eggs and tested for safety. It takes between three and six months to
manufacture large quantities of vaccines against the flu.
"By the time we realise it's a potential pandemic, it's too late," Wilson
said. "The timeliness of deploying the seasonal flu vaccine approach for
pandemics is not the best way to go."
Vaccines, which prime the body to remember to attack incoming pathogens, also
don't do the best job of protecting people who have diminished immune function,
such as seniors and those with chronic health problems.
The new treatment, which is delivered through a nasal spray, gets around that
problem because it doesn't require the body to mount an immune attack.
Instead, the nasal spray contains many copies of small, harmless viruses
called adeno-associated viruses. The simple genome of these viruses can be
altered in the lab to carry instructions for making special proteins called
broadly neutralising antibodies.
Broadly neutralising antibodies are rare super antibodies that are capable of
disarming many kinds of flu strains.
When researchers insert the instructions for making those antibodies into the
genome of adeno-associated viruses, the viruses act like Trojan horses. They
infect cells in the nose, inject the altered genetic material and turn the cells
into factories that crank out many copies of the broadly neutralising
"The way I envisioned it was sort of a bioshield," Wilson said. "I wanted to
focus the production of the antibody to the site where flu enters our body."
In animal tests, researchers showed that mice, ferrets and monkeys made many
copies of the super antibody after they inhaled the gene therapy treatment. And
the protection seemed to last for a while. Experts note, however, that promising
research in animals often does not pan out in humans.
"In mice, it persists up to a year," Wilson said. "In monkeys, we think we're
going to see expression up to six months."
The treatment also appears to work pretty quickly. Wilson said the animals
were fully protected about three days after their nasal passages were
In the test, treated and untreated mice and ferrets were exposed to several
different flu strains that have caused worldwide epidemics, including the
notorious H1N1 strain that caused the 1918 pandemic, which killed somewhere
between 30 million and 50 million people.
"The amount of virus we gave them is 100-fold more than would normally kill
them if they weren't treated," Wilson said.
Untreated animals quickly succumbed to the virus, but most animals treated
with the gene therapy had some protection against the flu strains they were
exposed to. Between 50% and 100% of the animals survived.
Importantly, 100% of the treated animals survived the H1N1 strains that
caused the 2009 and 1918 pandemics.
"It really shows that the antibody, when delivered the right way, really has
the ability to block infection and prevent disease," said Wilson, who said he
has a financial stake in the technology used to deliver the gene therapy.
Other researchers praised the study, but said many questions still need to be
answered before it can be used safely in humans.
"It is promising," said Dr Dimitrios Moskofidis, a virologist and
immunologist at Georgia Regents University in Augusta. "The question is, how
long could this protection last?" he said, and whether it's safe to coax
non-immune cells into making immune proteins.
Study author Wilson said the next step to try to answer those questions
involves human pilot studies, in which people would be given the gene therapy
treatment and then exposed to weakened flu viruses to see if they get sick.
If it works with the flu, Wilson said, it might work for other respiratory
For more information on flu vaccines, head to the US
Centers for Disease Control and Prevention.