30 May 2007
Human Antibodies Shown To Protect Mice from Avian Flu
China, Indonesia report new human cases, bringing total to 308
Washington -- An international team of scientists has reported using antibodies derived from immune cells from recent human survivors of highly pathogenic H5N1 avian influenza to treat H5N1-infected mice and to protect them from an otherwise lethal dose of the virus.
The research is a collaboration among scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, the Institute for Research in Biomedicine in Switzerland and the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Vietnam.
“If the success of this initial study is confirmed through further laboratory and clinical trials,” said NIAID Director Anthony Fauci in a May 28 statement, “human monoclonal antibodies could prove to be valuable therapeutic and prophylactic [preventive] public health interventions for pandemic influenza.”
Monoclonal antibodies are special hybrid disease-fighting proteins created in the laboratory from natural substances in the body.
The announcement comes amid reports of new human cases of infection by the highly pathogenic avian flu virus in China and Indonesia. These cases bring total human cases since 2003 to 308, with 186 deaths. (See related article.)
According to a May 30 statement on the World Health Organization (WHO) Web site, the Chinese Ministry of Health reported a new case of human H5N1 infection that the national laboratory there confirmed May 23.
A 19-year-old soldier serving in Fujian province developed fever and pneumonia-like symptoms May 9 and was hospitalized May 14. He does not seem to have had contact with sick birds. Individuals with whom he had close contact are under medical observation; of 25 cases confirmed in China, 15 have been fatal.
In Indonesia, the Ministry of Health reported a new human case of H5N1 infection in a 5-year-old girl from Wonogiri district in Central Java Province. She developed symptoms May 8, was hospitalized May 15 and died two days later. Initial investigations indicate she was exposed to dead poultry. Of 97 cases confirmed in Indonesia, 77 have been fatal. (See related article.)
The immune system recognizes foreign substances -- like disease-causing viruses -- as invaders called antigens. Natural defenses against antigens are antibodies, proteins that seek out antigens and help destroy them.
Antibodies are specific -- each binds to and attacks one particular antigen. Once some antibodies -- like those for chickenpox and measles -- are activated, they keep protecting people from those diseases. This characteristic makes it possible to develop vaccines, according to the U.S. National Health Museum.
Monoclonal antibody technology lets scientists produce large amounts of pure antibodies by obtaining cells that produce antibodies naturally. They also use a class of cells that are “immortal,” that is, they grow continually in cell culture.
If scientists use these cells to form a hybrid that combines the characteristic of immortality with the ability to produce the desired substance, they have a biological factory that produces antibodies around the clock.
In monoclonal antibody technology, tumor cells that replicate endlessly are fused with human cells that produce an antibody. The result of this cell fusion is a "hybridoma" that continually produces antibodies.
PROTECTION FROM H5N1
In the work that produced human antibodies to protect mice from H5N1, four Vietnamese adults diagnosed with H5N1 flu infection between January 2004 and February 2005 agreed to donate blood soon after they recovered.
In Switzerland, Dr. Antonio Lanzavecchia extracted antibody-producing white blood cells from the Vietnamese samples and treated them with a process he developed so they produced large amounts of antibody.
Next, researchers in Dr. Kanta Subbarao’s NIAID lab screened 11,000 antibody-containing samples provided by the Swiss team and found a handful able to neutralize H5N1 flu virus.
Based on these results, Lanzavecchia created four monoclonal antibodies that secrete H5N1-specific neutralizing antibodies.
Subbarao and co-workers first tested whether the human H5N1 monoclonal antibodies could protect mice from severe H5N1 infection.
The mice receiving non-H5N1 monoclonal antibodies developed severe illness and died within a week. Those receiving the first H5N1 monoclonal antibody tested survived, and 80 percent of mice receiving the highest dose of the second H5N1 monoclonal antibody survived.
The scientists also tested the therapeutic potential of the human H5N1 monoclonal antibodies. Using blood products from flu survivors is an old idea, they said.
During the flu pandemic of 1918-1919, for example, physicians took serum from recovered flu patients and gave it to new victims; recent historical research indicates that those blood transfusions, when given early in the illness, sometimes saved lives.
Taken together, Subbarao said, the research findings show that fully human monoclonal antibodies with potent H5N1 flu virus neutralizing ability can be generated quickly from the blood of convalescent patients, and that the monoclonal antibodies work well to treat H5N1 infection and prevent death from such infection, at least in mice.
The authors plan to take the research forward by scaling up the production of H5N1 monoclonal antibodies and, if the technique is safe and effective in more animal tests, to evaluate the human monoclonal antibodies in clinical trials in people.
Additional information about flu is available at the NIAID Web site.
For more information on U.S. and international efforts to combat avian influenza, see Bird Flu (Avian Influenza).
(USINFO is produced by the Bureau of International Information Programs, U.S. Department of State. Web site: http://usinfo.state.gov)
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