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Painting by Marta Murphy - Bjorkman Lab
Researchers from the Townsend Group have collaborated with the Howarth Lab (University of Cambridge) and the Bjorkman Group (Caltech) to develop an improved version of a novel all-in-one vaccine against coronavirus threats. Results from this study have been published in the journal Nature Nanotechnology.
Previous work by the Townsend and Bjorkman groups contributed to the development of a nanoparticle vaccine (Mosaic-8b RBD-mi3), which was able to target multiple different types of SARS-like betacoronaviruses (sarbecoviruses). This vaccine should enter Phase 1 clinical trials early next year. However, the complex nature of this vaccine makes it challenging to manufacture, which could limit large-scale production of the vaccine in the future. In this new study, the authors present an updated version of the vaccine that should be simpler to make.
The Mosaic-8 vaccine developed previously featured Receptor Binding Domains (RBDs) from eight different coronaviruses. RBDs are parts of the viral spike protein that are targeted by antibodies, host proteins that are raised by the immune system in response to pathogens. These eight RBDs were ‘glued’ onto a nanocage structure, allowing one vaccine to present the eight different domains and generate an immune response. The Mosaic-8 vaccine was shown to provide protection against a diverse range of sarbecoviruses, not just the eight with RBDs included in the vaccine.
Figure showing assembly of Mosaic-8 (top) versus Quartet Nanocage (bottom) vaccines: Single RBDs or Quartets are ‘glued’ to the “SpyCatcher003-mi3" Nanocage.
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In the new study, led by Professors Howarth, Townsend and Bjorkman, the authors introduce a new version of the Mosaic-8 vaccine, which they named a Quartet Nanocage vaccine. For the new vaccine, the researchers fused RBDs from four different coronaviruses to make one protein molecule, called a Quartet. The Quartet molecules were then ‘glued’ to the same nanocage structure used previously for the Mosaic-8 vaccine. By making two different Quartets and attaching them to the nanocage, researchers could once again manufacture a vaccine that displays RBDs from eight viruses. However, this time, only three different components needed to be prepared (two Quartets and one nanocage) rather than nine as in the Mosaic-8 (eight RBDs and one nanocage), simplifying the vaccine manufacturing process. |
The new Quartet Nanocage vaccines were able to produce a level of immune responses and protection against coronaviruses that were similar, if not better, than the Mosaic-8 vaccine. Another advantage of the Quartet Nanocages is the ability to display more RBDs. The Quartet Nanocage design allows four RBDs to be displayed from one site on the nanocage, rather than needing four individual sites as is the case with the Mosaic-8 design.
Rory Hills, first author of the paper, said:
We have shown that a relatively simple vaccine can produce a protective response for several coronaviruses. This is an important step towards our goal of creating vaccines for pandemic threats before they are able to infect humans.
Read the full paper here: https://www.nature.com/articles/s41565-024-01655-9
Hear from first author Rory Hills in this video produced by the Department of Pharmacology, University of Cambridge: https://youtu.be/UCQl4dBttOg