text: Researchers determined the crystal structure of the FI6 antibody when it was bound to H1 and H3 HA proteins. Sitting atop the HA spike is a globular head domain that binds to cellular receptors during viral entry and contains the major antigenic sites targeted by the immune system. Because of this selective pressure, the sequence in the head domain drifts enough to require an updated seasonal vaccine most years. A stalk domain connects the head to the viral membrane and is responsible for fusing viral and host membranes so that the pathogen can invade human cells. The immune system usually does not have a strong response to the partially hidden stalk domain, so portions of the stalk remain highly conserved across all influenza subtypes. The FI6 antibody makes extensive contacts with conserved parts of the stalk, thereby blocking HA from harpooning a sticky fusion peptide into the host membrane during viral entry.
  The FI6 provides scientists with a broadly neutralizing antibody that recognizes all 16 HA subtypes, including emerging ones, such as H5N1. But, because the replication of the influenza virus is somewhat error-prone, the virus evolves as a quasispecies, and widespread use of antiviral drugs can lead to resistant strains. Such has been the case for oseltamivir and for the M2 ion channel blocker amantadine. Therefore, before considering FI6 as long-term prophylactic or therapeutic agent against seasonal influenza, we would first have to determine whether the influenza virus could quickly mutate the epitope targeted by FI6 and escape recognition by FI6 after exposure.
  A more important clinical implication of this work is the identification of a universal neutralizing epitope in the HA stalk at the atomic level an important intellectual landmark for the development of a universal influenza vaccine. In the absence of the immunodominant head domain, isolated portions of the HA stalk that include the FI6 epitope and  have already been shown to stimulate broad, but not universal, protective effects against H1N1 and H3N2 strains in vaccinated animals. Using protein engineering and adjuvants to focus the immune system on the FI6 epitope may be the critical next step along the path to a universal vaccine.