Monoclonal antibodies effective against bird flu, seasonal flu

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 Dr. Ruben Donis, 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 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.

Seasonal influenza occurs each year, causing mild to severe illness. Worldwide, more than 250,000 deaths from seasonal influenza occur annually. The best protection from seasonal influenza is yearly vaccination.

Influenza pandemics are worldwide outbreaks of disease that occur when a new influenza virus emerges for which people have little or no immunity. The disease spreads easily person-to-person, causes serious illness, and can spread across the country and around the world in a very short time. Health professionals are concerned that the continued spread of a highly pathogenic avian influenza A (H5N1) virus across eastern Asia and other countries represents a significant threat to human health. While vaccines can control influenza, they are not always effective because the vaccine must be updated each year. Vaccines against H5N1 in development have shown promise, but none has been reported to elicit a broad response in humans that would cover a broad range of different H5N1 virus strains. Antiviral medications, including the neuraminidase inhibitor oseltamivir (Tamiflu ®), is the primary treatment method, but has limited effectiveness if administered more than 24-48 hours after symptom onset.

-read more in J. Sui et al., “Structural and Functional Bases for Broad-spectrum Neutralization of Avian and Human Influenza A Viruses,” Nature Structural & Molecular Biology (DOI: 10.1038/nsmb.1566) (2009)