Ian A. Wilson
Hansen Professor of Structural Biology
Chair of the Department of Integrative Structural and Computational Biology
The Scripps Research Institute
San Diego, CA
Broadly Neutralizing Antibody Assisted Design of Peptide-based Inhibitors of Influenza Virus
Influenza virus remains a constant threat to global health. The 1918 H1N1 pandemic caused around 50 million deaths worldwide and up to 30–50% mortality has been reported for emerging viruses, such as H5N1 and H7N9. Therefore, there is an urgent need to design a much more effective vaccine and therapies to protect against the multiple strains and types of influenza virus.
Until relatively recently, it was thought that antibodies to influenza virus could protect only against highly related strains within the same subtype. However, since 2008, many potent human broadly neutralizing antibodies, bnAbs, have been isolated that target the hemagglutinin glycoprotein, HA. These antibodies bind to highly conserved functional sites on the HA—the stem, fusion domain, and receptor binding site—and have revealed common motifs for HA recognition despite different antibody origins and germlines.
This structural and functional characterization of human bnAbs against the HA is now providing exciting new opportunities for design of novel vaccines and new therapeutics that afford greater protection against influenza virus. I will discuss antibody-inspired design, structure and properties of peptides as inhibitors of influenza virus. Some of the work 1 was done in collaboration with Janssen Prevention Center, Leiden, Netherlands.
AuthorsIan A. Wilson
AffiliationsDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA
1. Kadam RU, Juraszek J, Brandenburg B, Buyck C, Schepens WBG, Kesteleyn B, Stoops B, Vreeken RJ, Vermond J, Goutier W, Tang C, Vogels R, Friesen RHE, Goudsmit J, van Dongen MJP, Wilson IA. Potent peptidic fusion inhibitors of influenza virus Science, 2017; 358:496–502