This week, we profile a recent publication in Nature from Daniel Ellis (pictured)
and Dr. Neil King at the UW Institute for Protein Design.
Can you provide a brief overview of your lab’s current research focus?
The King lab is broadly focused on designing and functionalizing protein-based nanomaterials for medical development. Our main focus is protein nanoparticles, or tiny little defined shapes (1/40th the width of a bacterial cell) that can be engineered for various molecular tasks. Some of our lab is focused on making vaccines using protein nanoparticles, while others are focused more on delivering molecular cargo (drugs, RNA, protein, polymers) packaged inside the particles. Because we are all very interested in designing and/or re-engineering proteins, many other protein engineering projects have naturally spun off too, including stabilizing viral antigens (isolated pieces of viruses that are often unstable when studied outside of the viral context) for vaccines, and designing custom-made proteins capable of interacting with various immunological receptors, which could aid vaccine research or immunotherapies. It is a very creative work environment, and there are not really any formal bounds.
What is the significance of the findings in this publication?
This publication aimed to make a better version of seasonal influenza vaccines. Current influenza vaccines have four key pieces, which are distinct hemagglutinin (HA) antigens derived from four different lineages of influenza that currently circulate. Current vaccines do a great job of eliciting antibodies against the four HAs in the vaccine, but have sharp drop offs in effectiveness when annual predictions of circulating viruses are not accurate.
We attached the same four HAs to one of our protein nanoparticles and, in collaboration with the NIH Vaccine Research Center (credit to many, most particularly co-author Seyhan Boyoglu-Barnum and her mentors, Masaru Kanekiyo and Barney Graham) found that reorganizing the pieces of current vaccines around the nanoparticle leads to higher quality antibody responses in many ways. The antibody responses against the viruses represented in the vaccine were as good if not slightly better then current vaccines. This is great, because current vaccines are very effective when “on-target”.
What surprised us is that our nanoparticle vaccines elicited antibody responses that recognized many more viruses than current vaccines, included mismatched seasonal viruses that represent threats seen during a bad flu season with poor prediction of circulating viruses. Further, we found that the nanoparticle vaccines elicited responses to distantly related avian viruses, such as H5N1 and H7N9, which are considered possible pandemic threats. We dug deeper into the precise details of the antibodies, and found that a minor but important portion of the antibodies elicited by our nanoparticle vaccines were focused on a highly conserved part of HA, called the stem. Current vaccines do not elicit such responses in protective quantities, while the nanoparticle vaccines did.
In all, it appears possible to simply reorganize the pieces of current vaccines using our protein nanoparticles to make a vaccine that could not only provide protection against bad flu seasons, but possibly even an influenza pandemic.
This work was funded by:
- The intramural research program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- A gift from the Open Philanthropy Project
- A gift from the Audacious Project
- Defense Threat Reduction Agency (HDTRA1-18-1-0001)
- The National Institute of General Medical Sciences (R01GM120553)
- The National Institute of Allergy and Infectious Diseases (DP1AI158186 and HHSN272201700059C)
- A Pew Biomedical Scholars Award
- Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund
- Article the National Institute of General Medical Sciences (R01GM099989)
- The University of Washington Arnold and Mabel Beckman Cryo-EM Center
