Universal protection from nearly all flu strains may be just a nose spray away.
A type of gene therapy developed for use in HIV-positive patients and altered to work in the respiratory system as a treatment for cystic fibrosis has been adapted to confer broad protection against pandemic flu strains by researchers at the University of Pennsylvania School of Medicine.
In lab tests using mice and ferrets, the spray helps the body fight off a variety of flu strains, including the H1N1 Spanish Influenza virus from 1918 that killed as many as 40 million people as well as the more recent H1N1 pandemic from 2009. The research was published in the journal Science Translational Medicine.
The process is different from a standard vaccine, which uses weakened strains of a flu virus to stimulate the body to create antibodies. In seasonal vaccines, that process can prove ineffective, because scientists have to predict how the virus will mutate before it does. If they choose the wrong strains, the vaccine offers little protection.
A few years ago, James Wilson, who designed the new therapy, and Bill Gates were discussing alternative ways to fight potential pandemic outbreaks of various diseases. In HIV patients, injections of reprogrammed viruses were given to patients to stimulate the body to create the antibodies necessary to fight the disease. Wilson thought that, maybe, the gene therapy could be used to stimulate the body to create antibodies that are widely effective against the flu.
"The idea with HIV was that you'd inject the [virus] into the muscle and then when someone was exposed to HIV, they would already have the antibodies necessary to prevent the infection," Wilson says. "Following that, I began to consider ways to use that process against respiratory pathogens."
Wilson says that, because the flu is nearly always passed through the respiratory tract, a nasal spray would make more sense than an injection. In his latest experiment, mice and ferrets breathed in a small amount of a vector designed to stimulate their nasal epithelial cells (which line the inside of the nose and respiratory system) to express antibodies.
"If the pathogen was transmitted through a respiratory route, it seemed a better way to proceed was to deliver the vector and have it be expressed at the site where the pathogen enters our body," he says. "We engineered the cells that lined the airway to express those antibodies, even though they don't normally."
Mice and ferrets given the nasal spray seemed to be protected from the flu within a matter of days – with standard flu vaccines, it can take as long as two weeks for antibodies to develop. Those exposed to normally lethal viruses were either able to fight the viruses off quickly or didn't show any signs of infection.
"It works like a biomask – we get a high concentration of antibodies right where the virus enters the body," he says. "We're trying to achieve universal protection. We wanted to determine how effective it'd be across as many strains of pandemic flu as we could get our hands on."
Wilson says that in animals, the spray provides about 9 months of protection. In humans, he expects that it'd last for about 6 months, could be used as a replacement for standard flu vaccines and could be quickly delivered in case of a pandemic outbreak. The treatment, he says, could be expanded to diseases beyond the flu and could be quickly passed out in the case of biological warfare.
"We could make it in advance of a pandemic – if we had an antibody that we think could be protective, we could already have them made," he says. "Once we establish the principle of antibody into the nasal administration, then it's like a cassette, we can just put another antibody into the same platform."