Gene therapy may protect against pandemic flu strains

U.S. researchers said Wednesday they have developed a new gene therapy that in animal studies can provide broad protection against flu viruses associated with historic human pandemics. If confirmed in humans, the approach could be used to shield populations from an emerging pandemic, or protect the elderly and other high-risk populations from the seasonal flu. The findings, described in a study in the journal Science Translational Medicine, involved using powerful molecules known as broadly neutralizing antibodies that can disable a wide range of viruses and packaged them into an adeno-associated virus (AAV) vector, most commonly used to deliver genes in gene therapy. Researchers then injected the virus vectors containing the antibodies into the nasal passages of mice that were exposed to lethal quantities of three strains of H5N1 and two strains of H1N1. All the strains were associated with historic human pandemics, including the infamous 1918 H1N1 that killed as many as 40 million people. Flu virus rapidly replicated in untreated animals all of which needed to be euthanized. However, pretreatment with the AAV vectors virtually shut down virus replication and provided complete protection against all strains of flu in the treated animals. The efficacy of this approach was also demonstrated in ferrets, which provide a more authentic model of human pandemic flu infection, the researchers said. "The novelty of this approach is that we're using AAV and we're delivering the prophylactic vaccine to the nose in a non-invasive manner, not a shot like conventional vaccines that passively transfer antibodies to the general circulation," said Maria Limberis, assistant professor at the University of Pennsylvania and one of the authors of the study, in a statement. James Wilson, director of the gene-therapy study, said the accomplishment is a "critical proof-of-concept." "Further development of this approach for pandemic flu has taken on more urgency in light of the spreading infection in China of the lethal bird strain of H7N9 virus in humans," Wilson added. Although the results are promising, the researchers noted more work is needed to determine the safety of this approach in humans and how long it offers protection before re-administration is needed.