New weapon in battle against flu pandemic

Published on Sunday 22 February 2009 22:25

THE discovery of proteins that neutralise a wide range of viruses, including deadly pandemic strains, could represent a breakthrough in the fight against flu.

Scientists screened a "library" of billions of antibodies and identified ten that target an "Achilles heel" present in most harmful forms of influenza.

The weak spot is the "neck" of the virus, just below its peanut-shaped head. By attaching to this point, the antibodies stop the virus undergoing a vital shape-change that allows it to infect cells.

New drug treatments based on the proteins could be several years away. But if future development proves successful, they would have the potential to save thousands if not millions of lives during a serious flu pandemic.

Doctors are worried that, in the event of a pandemic – for instance, by an easily transmitted version of H5N1 bird flu – many people would die before a vaccine became available.

However, the synthetic "monoclonal" antibodies could be rapidly deployed during the four to six months it would take to produce a suitable vaccine.

Antibody therapy could also be used to protect vulnerable people such as the sick and elderly from seasonal flu outbreaks.

Dr Wayne Marasco, one of those who led the research, said: "There are clear settings where human monoclonal antibodies can be used strategically for both the prevention and early treatment of influenza infection and disease.

"At-risk individuals, such as first responders and medical personnel, exposed family members and co-workers, and patients who cannot make antibodies because of pre-existing medical conditions or advanced age, could all benefit from this new type of therapy."

Dr Marasco's team discovered and described the atomic structure of the viral "Achilles heel" and showed how it offered a new way of attacking flu.

The ten antibodies identified neutralised all Group 1 influenza A viruses, including H5N1 bird flu, the 1918 pandemic "Spanish Flu" strain that killed an estimated 50 million people around the world, and seasonal H1N1 strains.

Professor Robert Liddington, one of the study's co-authors, said: "The head portion of haemaglutinin is highly mutable, leading to the rise of forms of the virus that can evade neutralising antibodies.

"However, the stem region of haemaglutinin is highly conserved because it undergoes a dramatic conformational change to allow entry of viral RNA (a genetic molecule] into the host cell.

"It's very difficult to get a mutation that doesn't destroy that function, which explains why we aren't seeing escape mutants and why these antibodies neutralise such a variety of strains of influenza."

The research is published online in the journal Nature Structural & Molecular Biology.