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Flu Virus May Have an Achilles Heel

Researchers discover a natural human antibody that may be the Trojan horse to defeat the flu.


 

The flu virus uses a hemagglutinin (HA) protein to enter and infect cells. The “head” of the protein was thought to be safe from antibody attacks.

Turns out, it has a previously unsuspected chink in its armor. And researchers from National Institute of Allergy and Infectious Diseases may have found an “unexpected new target” for antiflu therapies. They discovered a naturally occurring human antibody (FluA-20) that—to their surprise—binds to the head of the HA protein at a site that was not thought to be vulnerable.

Using FluA-20 isolated from a patient who had received many influenza immunizations, the researchers showed that FluA-20 “reaches into” an otherwise inaccessible part of the HA trimer molecule and “rapidly disrupts” its integrity. In other words, FluA-20 causes it to fall apart, preventing the spread of virus.

Although the researchers also discovered that the window of opportunity is narrow (the region is only briefly exposed to antibody attack), unlike the rest of HA’s head, the open-access region varies little among influenza strains. The critical HA residues recognized by FluA-20, the researchers say, remain conserved across most subtypes of influenza A virus, which explains the antibody’s “extraordinary breadth.” In mouse studies, when used as prophylaxis or therapy, it protected against H1N1, N3N2, H5N1, and H7N9 subtypes.

In theory, the researchers say, direct strikes with antibody-based therapeutics against that part of the HA protein could be effective with many strains of influenza A virus, and—also theoretically—other influenza strains.

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