Human Antibodies Neutralize Avian Flu

Professor Robert Liddington (Credit: Burnham Institute for Medical Research)

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 very quickly; moving from person to person and can affect whole countries. Many health professionals are concerned that the spread of avian flu throughout eastern Asia presents a significant threat to human health. Worldwide, more than 250,000 deaths from seasonal influenza occur annually. Current treatment methods include vaccines which have to be updated yearly and anti-viral medications which only have limited effectiveness.

Researchers at the Dana-Farber Cancer Institute, Burnham Institute for Medical Research, and the Centers for Disease Control and Prevention have discovered that monoclonal antibodies (mAb) neutralize an unprecedented range of influenza A viruses, including avian influenza A (H5N1) virus, previous pandemic influenza viruses, and some seasonal influenza viruses. The team identified antibodies that neutralize a broad range of influenza A subtypes. The antibodies bind to a highly conserved stem area in the H5 type hemagglutinin (HA). Once they bind to the stem, the virus cannot change to a conformation, which is necessary in order to enter the host cell. This prevents further infection of host cells and the proliferation of virus mutants. The research showed that a great number of different types of bird flu were inhibited by the mAb and that mAbs protected mice that were exposed to the H5N1 virus even when injected three days after the infection.

Crystal structure of influenza hemagglutinin H5 bound to a potent antibody (F10, in red) capable of neutralizing more than half of all strains of influenza virus (Credit: Burnham Institute)

“The head portion of hemagglutinin is highly mutable, leading to the rise of forms of the virus that can evade neutralizing antibodies,” said Robert Liddington, Ph.D, one of the investigators on the study. “However, the stem region of hemagglutinin is highly conserved because it undergoes a dramatic conformational change to allow entry of viral RNA into the host cell. It’s very difficult to get a mutation that doesn’t destroy that function, which explains why we aren’t seeing escape mutants and why these antibodies neutralize such a variety of strains of influenza.”