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23/02/2009 02:08:05
France-New Vaccine for bird flu.
Scientists on Sunday unveiled lab-made human antibodies that can disable several types of influenza, including highly-lethal H5N1 bird flu and the "Spanish Flu" strain that killed tens of millions in 1918.
Tested in mice, the antibodies work by binding to a previously obscure structure in the flu virus which, when blocked, sabotages the pathogen’s ability to enter the cell it is trying to infect, according to the study.
Because this structure -- described by one scientist as a "viral Achilles’ heel" -- is genetically stable and has resisted mutation over time, the antibodies are effective against many different strains.
The breakthrough "holds considerable promise for further development into a medical tool to treat and prevent seasonal as well as pandemic influenza," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which helped fund the study.
Clinical trials on humans could begin within a couple of years, the researchers said.
Seasonal flu kills more than 250,000 people every year, and pandemic flu, which occurs with the emergence of deadly viral strains against which people lack immunity, remains an ever-present threat.
Vaccines have long been the first line of defense against flu, but even seasonal viruses evolve so rapidly that the vaccines need to be updated every year. Even then, they are not always effective.
A team led by Wayne Marasco, a professor at Harvard Medical School, began the study by scanning tens of billions of so-called monoclonal antibodies in the laboratory.
Antibodies, produced by the immune system’s white blood cells, are highly specialised proteins that seek out and bind to other large molecules, called antigens, found on the surface of an invading bacteria or virus.
Once locked in, an antibody serves as a beacon to immune cells that attack the pathogens. More rarely, it can disable a disease agent all by itself.
Monoclonal antibodies are manufactured in the laboratory from a single parent cell using a technique devised more than 30 years ago.
In cancer treatment, they help the immune system zero in on the right target.
Marasco and colleagues turned up 10 of the artificial antibodies that bound to the H5N1 avian flu, said the study, published in the Nature Group’s journal Nature Structural and Molecular Biology.
In further experiments with mice, the scientists found that three of these monoclonal antibodies neutralised 10 of 16 known influenza "A" viruses, including H5N1.
To date, only persons in close contact with infected fowl have become infected with this deadly strain. But scientists fear that a future mutation could "jump species" and become easily transmissible among humans.
These were startling results. Not only had a single type of antibody honed in on different strains of virus, it had disarmed the pathogens on its own without having to call in immune system reinforcements.
To find out how this was possible, Marasco teamed up with researchers at the Infectious and Inflammatory Disease Center in La Jolla, California to analyse the atomic structure of one of the antibodies.
They discovered that by latching onto a poorly understood part of a lollipop-shaped protein -- called hemagglutin (HA) -- on the surface of the virus, the lab-made antibody had disabled the pathogen’s capacity to change shape and thus enter into the host cell.
"We believe ... the hemagglutin protein acts as a decoy by constantly undergoing mutation and thereby attracting the immune system to produce antibodies against it rather than against the pocket in the neck of the protein," Marasco said a statement.
In a commentary, also published by Nature, Taia Wang and Peter Palese of the Mount Sinai School of Medicine in New York said the study had uncovered "a viral Achilles’ heel" that is resistant to genetic variation.
The new findings "brings us closer to the development of a universal influenza virus vaccine," they said.
Tested in mice, the antibodies work by binding to a previously obscure structure in the flu virus which, when blocked, sabotages the pathogen’s ability to enter the cell it is trying to infect, according to the study.
Because this structure -- described by one scientist as a "viral Achilles’ heel" -- is genetically stable and has resisted mutation over time, the antibodies are effective against many different strains.
The breakthrough "holds considerable promise for further development into a medical tool to treat and prevent seasonal as well as pandemic influenza," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which helped fund the study.
Clinical trials on humans could begin within a couple of years, the researchers said.
Seasonal flu kills more than 250,000 people every year, and pandemic flu, which occurs with the emergence of deadly viral strains against which people lack immunity, remains an ever-present threat.
Vaccines have long been the first line of defense against flu, but even seasonal viruses evolve so rapidly that the vaccines need to be updated every year. Even then, they are not always effective.
A team led by Wayne Marasco, a professor at Harvard Medical School, began the study by scanning tens of billions of so-called monoclonal antibodies in the laboratory.
Antibodies, produced by the immune system’s white blood cells, are highly specialised proteins that seek out and bind to other large molecules, called antigens, found on the surface of an invading bacteria or virus.
Once locked in, an antibody serves as a beacon to immune cells that attack the pathogens. More rarely, it can disable a disease agent all by itself.
Monoclonal antibodies are manufactured in the laboratory from a single parent cell using a technique devised more than 30 years ago.
In cancer treatment, they help the immune system zero in on the right target.
Marasco and colleagues turned up 10 of the artificial antibodies that bound to the H5N1 avian flu, said the study, published in the Nature Group’s journal Nature Structural and Molecular Biology.
In further experiments with mice, the scientists found that three of these monoclonal antibodies neutralised 10 of 16 known influenza "A" viruses, including H5N1.
To date, only persons in close contact with infected fowl have become infected with this deadly strain. But scientists fear that a future mutation could "jump species" and become easily transmissible among humans.
These were startling results. Not only had a single type of antibody honed in on different strains of virus, it had disarmed the pathogens on its own without having to call in immune system reinforcements.
To find out how this was possible, Marasco teamed up with researchers at the Infectious and Inflammatory Disease Center in La Jolla, California to analyse the atomic structure of one of the antibodies.
They discovered that by latching onto a poorly understood part of a lollipop-shaped protein -- called hemagglutin (HA) -- on the surface of the virus, the lab-made antibody had disabled the pathogen’s capacity to change shape and thus enter into the host cell.
"We believe ... the hemagglutin protein acts as a decoy by constantly undergoing mutation and thereby attracting the immune system to produce antibodies against it rather than against the pocket in the neck of the protein," Marasco said a statement.
In a commentary, also published by Nature, Taia Wang and Peter Palese of the Mount Sinai School of Medicine in New York said the study had uncovered "a viral Achilles’ heel" that is resistant to genetic variation.
The new findings "brings us closer to the development of a universal influenza virus vaccine," they said.
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