Researchers close in on possible flu foe
Scientists identify human monoclonal antibodies to fight bird and seasonal flu viruses.
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BOSTON—It may not be the silver bullet that ultimately kills the flu, but researchers at the Dana-Farber Cancer Institute, the Burnham Institute for Medical Research of La Jolla, Calif., and the Atlanta-based Centers for Disease Control and Prevention (CDC), have engineered human antibodies to attack influenza viruses and reduce the threat of not only suffering from flu symptoms every year, but also preventing a future pandemic.
The key to this discovery came when scientists identified a monoclonal antibody (mAb) that neutralizes an unprecedented range of influenza A viruses, including the avian influenza A (H5N1) virus, previous pandemic influenza viruses and some seasonal influenza viruses, according to a study published online Feb. 22 in Nature Structural and Molecular Biology. An estimated 250,000 people worldwide perish from seasonal flu each year.
Dr. Wayne A. Marasco, associate professor of medicine at Dana-Farber and Harvard Medical School, says researchers may have found the Achilles heel for all kinds of influenza viruses.
The antibodies bind to the stem region of the H5 type hemagglutinin (HA), preventing viral entry into the host cell, further infection of host cells and the rise of escape mutants, Marasco says. This is crucial because until now, antivirals and vaccines have targeted the heads of the molecule, which has been ineffective since the head is constantly mutating, the reason why a new flu vaccine must be developed each year.
Vaccines consisting of attenuated or killed virus do not typically stimulate antibodies against the stem, perhaps because it is less accessible than the head region. In this study, the scientists used recombinant purified protein, not a virus, so the antigenic part of the virus recognized by the antibodies was fully exposed.
Marasco says he expects clinical trials to start in 2011 to 2112 winter seasons. While the development of a long-lasting flu vaccine may take longer, researchers are on the right track for vaccine research, he says.
Manufacturing costs may be less than expected since large pharmaceutical companies have built plants in recent years, and because people may need only one dose of the drug to be effective, researchers say.
The ultimate goal is to "get it into people and start saving lives right away," Marasco said.
Although researchers do not have a partner for the development and manufacture of the potential drug, one possibility, according to news reports, could be a partnership among private entities and the federal government.
While more costly to produce than existing influenza drugs, therapeutic antibodies can be readily manufactured and stockpiled. In the event of a pandemic, the antibodies could be used in combination with antiviral therapies to contain the outbreak until a vaccine became available, researchers say. The production of a new influenza vaccine takes six to nine months using conventional methods.
Dr. Robert Liddington, professor and director at the Infectious and Inflammatory Disease Center at Burnham, says he also believes the new antibodies will put a major hit on the flu, "an annual killer on a large scale."
Dr. Ruben Donis, chief of the Molecular Virology and Vaccines Branch at CDC, reports the human monoclonal antibody protected mice from the lethal H5N1 virus even when injected three days after infection.
"This is good news, but many antibodies can do this," Donis says. "What surprised us is that the same antibody protected mice from a lethal infection with a very different virus such as the H1N1 subtype that causes seasonal human infections. This is really remarkable."
The key to this discovery came when scientists identified a monoclonal antibody (mAb) that neutralizes an unprecedented range of influenza A viruses, including the avian influenza A (H5N1) virus, previous pandemic influenza viruses and some seasonal influenza viruses, according to a study published online Feb. 22 in Nature Structural and Molecular Biology. An estimated 250,000 people worldwide perish from seasonal flu each year.
Dr. Wayne A. Marasco, associate professor of medicine at Dana-Farber and Harvard Medical School, says researchers may have found the Achilles heel for all kinds of influenza viruses.
The antibodies bind to the stem region of the H5 type hemagglutinin (HA), preventing viral entry into the host cell, further infection of host cells and the rise of escape mutants, Marasco says. This is crucial because until now, antivirals and vaccines have targeted the heads of the molecule, which has been ineffective since the head is constantly mutating, the reason why a new flu vaccine must be developed each year.
Vaccines consisting of attenuated or killed virus do not typically stimulate antibodies against the stem, perhaps because it is less accessible than the head region. In this study, the scientists used recombinant purified protein, not a virus, so the antigenic part of the virus recognized by the antibodies was fully exposed.
Marasco says he expects clinical trials to start in 2011 to 2112 winter seasons. While the development of a long-lasting flu vaccine may take longer, researchers are on the right track for vaccine research, he says.
Manufacturing costs may be less than expected since large pharmaceutical companies have built plants in recent years, and because people may need only one dose of the drug to be effective, researchers say.
The ultimate goal is to "get it into people and start saving lives right away," Marasco said.
Although researchers do not have a partner for the development and manufacture of the potential drug, one possibility, according to news reports, could be a partnership among private entities and the federal government.
While more costly to produce than existing influenza drugs, therapeutic antibodies can be readily manufactured and stockpiled. In the event of a pandemic, the antibodies could be used in combination with antiviral therapies to contain the outbreak until a vaccine became available, researchers say. The production of a new influenza vaccine takes six to nine months using conventional methods.
Dr. Robert Liddington, professor and director at the Infectious and Inflammatory Disease Center at Burnham, says he also believes the new antibodies will put a major hit on the flu, "an annual killer on a large scale."
Dr. Ruben Donis, chief of the Molecular Virology and Vaccines Branch at CDC, reports the human monoclonal antibody protected mice from the lethal H5N1 virus even when injected three days after infection.
"This is good news, but many antibodies can do this," Donis says. "What surprised us is that the same antibody protected mice from a lethal infection with a very different virus such as the H1N1 subtype that causes seasonal human infections. This is really remarkable."
