Influenza A is a member of the orthomyxoviridae family. Along with other influenza viruses, it causes from 3-5 million severe illnesses annually. Control of influenza epidemics rely on vaccinations and some antivirals like Tamiflu, but due to antigenic drift, and hundreds of strains, they have been wickedly resistant to containment. Haemagglutinin (HA) is a glycoprotein embedded in the envelope of Influenza A, and is responsible for receptor binding and membrane fusion. Current antivirals often target the head of HA to prevent viral infection, but the head is highly variable which prevents antibody effectiveness over a wide range of the Influenza A viruses, and mutates quickly.
In a new article published in Nature, researchers chose to focus on a different part of Haemagglutinin—the stem. The stem is a more conserved area of the glycoprotein, and antibodies that target this region may have more cross-reactivity. A monoclonal antibody named 3E1 has previously shown reactivity to the HA stem region, and showed promise in blocking viral infection. In the latest research, it was confirmed that 3E1 binds to the stem of the viral glycoprotein, and it was shown that 3E1 is effective at neutralizing a wide range of H1N1 and H5N1 subtypes.
Modeling of the antigen and its binding action demonstrate that 3E1 attaches to a highly conserved region of HA with a complementarity value comparable to other antibodies that are being investigated as weapons against Influenza A. When it binds, it prevents a conformational change in HA, which prevents it from going from a pre-fusion state to a fusion state, denying the virus access to the cell.
Although there is still much research to be done on this antibody, it shows promise as a model for developing antibody-based therapies against pandemic flus due to the lower mutation rate of the stem, and wider range of sub strains that is can neutralize as compared to traditional antiviral therapies.
Read the full article here:
Elisa Hofmeister ‘18