Newly Identified Antibodies Neutralize Flu Viruses
Researchers have identified human monoclonal antibodies (mAb) that neutralize an wide range of influenza A viruses. It is important to note the avian influenza A (H5N1) virus, previous pandemic influenza viruses, and some seasonal flu viruses are included in this group. The team of researchers was led by Wayne Marasco, a professor at Harvard Medical School.
Seasonal flu kills more than 250,000 people every year. Several children have already died this year from the flu. Pandemic flu remains an ever-present threat. Our first line of defense against the flu has been vaccines. Seasonal viruses evolve rapidly and our vaccines have to be updated each year.
The body's white blood cells produces the antibodies in response to invading bacteria or virus infections. Antibodies are highly specialized proteins that seek out and bind specific antigens found on the surface of an invading bacteria or virus.
The newly identified mAb antibodies neutralize the influenza A subtypes by binding to the highly conserved stem region of H5 type hemagglutinin (HA). By binding to the stem, the antibodies prevent entry by the virus into the host cell. This prevents infection of the host and the rise of escape mutants.
"Our human monoclonal antibody protected mice from the lethal H5N1 virus even when injected three days after infection," said Ruben Donis, chief of the Molecular Virology and Vaccines Branch at CDC. "This is good news, but many antibodies can do this. 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."
These antibodies have the potential for prevention and treatment. Therapeutic antibodies are more costly to produce than existing influenza drugs. They can be manufactured and stockpiled to be used in the event of a pandemic. The antibodies could be used in combination with current antiviral therapies (for example Tamiflu) to contain the outbreak until a vaccine became available. The production of a new influenza vaccine takes six to nine months using conventional methods.
Attenuated or killed virus vaccines do not usually 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 virus, so the antigenic part of the virus recognized by the antibodies was fully exposed.
The study was published online Feb. 22 in Nature Structural & Molecular Biology.