Diridavumab, the alternative names CR6261, is a human monoclonal antibody direct against influenza A hemagglutinin. The CR6261 antibody was first discovered by the Scripps Institute and Crucell, a dutch biopharmaceutical company, and later developed by Janssen Pharmaceutical Companies of Johnson & Johnson under the trade name diridavumab. The antibody drug was developed for the treatment of influenza A because its VH region could recognizes and binds to the conserved domain of influenza virus HA. Most antibodies produced after exposure to influenza viruses can only neutralize a single virus subtype, but diridavumab can neutralize many strains from multiple subtypes. In 2011, an article reported that diridavumab could neutralize several subtypes of influenza virus with high affinity, so it received extensive attention from researchers. In 2012, researchers conducted a combined treatment study of diridavumab with other drugs such as Oseltamivir or Zanamivir. It has been found that combined drugs can provide additional affinity to compensate for the loss of affinity between HA and monoclonal antibodies due to mutations and improve the therapeutic effect of diridavumab. In 2017, diridavumab was used in a clinical phase II treatment trial for influenza A infection, but the results have not yet been disclosed.
Diridavumab is used to prevent influenza A virus infection by neutralizing the main protein hemagglutinin on the surface of the influenza virus. Because of the highly conserved amino acid sequences in the binding region, diridavumab can identify and neutralize most influenza viruses. The surface antigen of influenza A virus is the most likely to mutate, causing an influenza pandemic. The antigen proteins on the surface of influenza A virus are divided into hemagglutinin (HA) and neuraminic acid (NA). Hemagglutinin is a non-immune protein molecule that is reversible and specifically recognizable to sugar and its conjugates. Hemagglutinin, existing on the surface of influenza virus and measles virus, can attach to the hemoglobin of different animals and make the red blood cells (RBCs) agglutinate and endanger the body.
Fig.1 Mechanism of Action of Diridavumab