I’ve been working to get a closer look at both the attachment protein (HN) and the fusion protein (F) of the mumps virus. HN helps the virus attach to human cells and triggers F, which then fuses the virus with the cell—this is how infection begins and disease develops. My project initially focused only on F. In previous work with the measles virus (which also possesses both an attachment and fusion protein), we showed that immunizing animals with a stabilized version of the F protein provided strong protection—even better than what is achieved with the MMR vaccine. These findings indicate that F is a good vaccine candidate, but I decided to also look into HN, since we don’t yet know which of the two proteins—F or HN—is more important for protection against the mumps virus. 

The HN structure is fascinating. HN is described in the literature to form tetramers, meaning it is made up of four identical subunits. While structures of the HN head domain exist, they only show the protein as a monomer (a single subunit), not in its full tetrameric form. 

For my project, I found a way to keep HN in its native state, which could be important for vaccine design because it better mimics the form found on the actual virus. I confirmed the tetrameric form of the protein using electron microscopy. I then sent the purified HN tetramer to our collaborators at Columbia University, where it was used to immunize mice. The goal is to generate the first-ever anti-HN antibodies. These will help us better understand the protein, support vaccine development, and potentially be used as mumps therapeutics. As the immunization was successful, I am now preparing to generate the antibodies. These antibodies will also help me to solve the first tetrameric structure of the HN protein.