"There are clear settings where human monoclonal antibodies can be used strategically for both the prevention and early treatment of influenza infection and disease," said Wayne A. Marasco, M.D., Ph.D., associate professor of medicine at Dana-Farber and Harvard Medical School. "At-risk individuals, such as first responders and medical personnel, exposed family members and coworkers and patients who cannot make antibodies because of pre-existing medical conditions or advanced age, could all benefit from this new type of therapy."
In the study, the team of scientists used a human antibody phage display library to identify 10 mAb that bind to the stem of H5 type HA, the influenza protein responsible for viral entry into the host cell. The scientists determined the X-ray crystal structure of the mAb bound to the H5N1 HA, which showed that the heavy chain of the mAb inserts into a highly conserved pocket in the HA stem, inhibiting the conformational change required for membrane fusion and viral entry into the cell.
The scientists further showed that an unprecedented number of different types of bird flu and seasonal influenza viruses were inhibited and the mAb protected mice that were exposed to H5N1 virus. "Our 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. 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," said Ruben Donis, PhD, chief of the Molecular Virology and Vaccines Branch at CDC.
Vaccines consisting of attenuated or killed virus do not typically stimulate antibodies against the stem, perhaps because it is less accessible than t
|Contact: Bill Schaller|
Dana-Farber Cancer Institute