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Article Date: 18 Aug 2008 - 0:00 PDTScientists in the US recovered antibodies to the 1918 flu virus from elderly survivors of the pandemic, used them to create cell lines of monoclonal antibodies and then showed they were still potent by injecting them into infected mice that survived, whereas the controls did not. The researchers believe the antibodies could help develop effective treatments to use in case a similar virus breaks out again, and the technology could help develop antibodies against other viruses like HIV.
The study was the work of Dr James Crowe, professor of Pediatrics and director of the Vanderbilt Program in Vaccine Sciences, at Monroe Carell Jr Children's Hospital at Vanderbilt University, Nashville, Tennessee, and colleagues, is published online in the journal Nature.
The 1918 flu pandemic killed nearly 50 million people worldwide, including many healthy young adults. Many experts believe it is only a matter of time before another flu virus, the deadly H5N1 bird flu strain, strikes in a similar manner; all that needs to happen is for the virus to mutate to be easily passed on from human to human, at present humans can only catch it from infected birds.
So it is not surprising that scientists have been working hard to find as many ways of studying highly infectious and deadly flu viruses as possible, and the 1918 one in particular. In 2005, researchers from Mount Sinai and the Armed Forces Institute of Pathology in Washington DC managed to recover the virus from the bodies of people who died in the 1918 outbreak and whose bodies had been preserved in the frozen soil of Alaska.
Working with two other study leaders, Dr Christopher Basler, from the Mount Sinai School of Medicine, and Dr Eric Altschuler, from the University of Medicine and Dentistry of New Jersey at the New Jersey Medical School, Crowe took blood samples from 32 survivors of the 1918 pandemic who were aged between 91 and 101 years. All the blood samples reacted to the 1918 virus, which suggested they still had antibodies.
The researchers then extracted some extremely rare B cells that produce antibodies in the immune system from 8 of the blood samples and grew them in culture in the lab. Seven of the samples produced antibodies that reacted to a protein of the 1918 virus, suggesting the immune systems of their owners were "on standby" in case the virus broke out again.
Crowe, who was initially skeptical about the project, said he was amazed by the results:
"The B cells have been waiting for at least 60 years -- if not 90 years -- for that flu to come around again."
"It's the longest memory anyone's ever demonstrated," he added.
Crowe and colleagues then fused the cells that reacted the most strongly against the virus with "immortal" cells to make a cell line that produces identical clones of the original antibody (monoclonal antibodies). These also showed a strong reaction against the 1918 virus, plus they cross reacted with proteins from the 1930 swine flu that was related to the 1918 strain, but they did not react to more modern strains.
But the scientists still had to show these monoclonal antibodies were effective in live animals. So Crowe and colleagues worked with researchers at the US Centers for Disease Control and Prevention (CDC) in a final phase of the study where they infected mice with the 1918 flu strain and then gave them different doses of the antibodies. The mice given the lowest dose and the mice that were not given any (controls) died, but all the mice given the highest doses survived.
Crowe said he was surprised because age usually weakens immunity, but he said:
"These are some of the most potent antibodies ever isolated against a virus." "They're the best antibodies I've ever seen," said Crowe.
The antibodies that Crowe and his team have developed could be used to make treatments for flu strains similar to the 1918 one, and the technology could be used to develop antibodies against other viruses such as HIV, they said. But what is also important is the knowledge gained from doing work like this, said Crowe:
"The lessons we are learning about the 1918 flu tell us a lot about what may happen during a future pandemic."
Sources: Vanderbilt University Medical Center.
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作者:admin@医学,生命科学 2011-03-24 19:02
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