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More Coronaviruses? How Dodecahedral Nanoparticles Can Protect Us

A novel vaccine design involves dodecahedral platform nanostructures that can be transformed into virus-like particles by fusion with viral antigens and consequently be used in vaccines.

We finally have vaccines against SARS-CoV-2, the virus that causes COVID-19. But what about future coronaviruses?

SARS-CoV-2 belongs to the Betacoronavirus genus, together with at least twenty other species including MERS-CoV and SARS-CoV, which have caused outbreaks in people in the past and the bat coronavirus strains WIV1 and SHC014, which is “thought to represent an ongoing threat to humans” (Cohen et al.). Additionally, as we have seen with the emergence of new variants of SARS-CoV-2, viral mutation is a reality which we must take seriously in order to avoid future pandemics.

With this in mind, scientists are now exploring the possibility of creating “all-in-one” multivalent coronavirus vaccines using nanotechnology: a vaccine that provides immunity not only against existing prominent strains, but also against potential future emerging coronaviruses in humans. The technology that allows us to create such polyfunctional particles is patented as SpyTag/SpyCatcher and it became available in 2012 (Zakeri et al.).

As part of the process, proteins synthesized to be identical copies of antigens, certain distinctive features of the virus, spontaneously fuse with the sites on the dodecahedral protein cage. The antigens are tagged with SpyTags which form irreversible isopeptide bonds with the SpyCatcher cage within minutes!

This chemical pairing was actually discovered by looking at the bacterium Streptococcus pyogenes (Zakeri et al.). The bond formed is the same bond that links together amino acids in our bodies (hence an alternative name for a protein—polypeptide). Another cool thing about SpyTag/SpyCatcher is that the nanocage can be produced using E.coli, making the production of the vaccine much easier (Hsia et al.).

In Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice, Alexander Cohen and his colleagues utilized SpyTag/SpyCatcher to make vaccines exhibiting antigens from different coronavirus strains on the same nanoparticle, which they refer to as mosaic nanoparticles. They used the so-called receptor-binding domain (RBD) parts of the virus spike proteins that are usually the ones that initiate the uptake of the virus by the cell and are hence a major target for the immune system. The RBD’s used were from the SARS-2, RaTG13, SHC014, Rs4081, pang17, RmYN02, Rf1, and WIV1 coronaviruses, which are all human and bat SARS-like betacoronaviruses.

Some of the surprising findings from the paper were that (1) viral antigens attached to the SpyCatcher003-mi3 nanoparticle were more effective as a vaccine in that they elicited a stronger immune response than viral antigens in solution after a booster dose, (2) nanoparticles with antigens from different coronaviruses attached to the same particle not only taught the immune system to recognize the strains presented, but also improved the immune response to sarbecoviruses not present in the vaccine – for instance, “although SARS-2 RBD was not presented on mosaic-4b, antibody titers elicited by mosaic-4b immunization (yellow) were not significantly different from titers elicited by matched nanoparticle immunizations” (Cohen et al.).

Notably, according to Cohen and his colleagues’ study, being ill with COVID-19 did not improve people’s immunity to other coronaviruses, which highlights the significance of the mosaic vaccine research. As the quest for a SARS-Cov-2 vaccine is drawing to a close, the quest for pan-coronavirus vaccines is only beginning, and SpyTag/SpyCatcher Plug-and-Display nanoparticle-based vaccines are one of the most prominent candidates right now.


Work Cited

  1. Cohen, Alexander A., et al. “Mosaic Nanoparticles Elicit Cross-Reactive Immune Responses to Zoonotic Coronaviruses in Mice.” Science, vol. 371, no. 6530, American Association for the Advancement of Science, Feb. 2021, pp. 735–41., doi:10.1126/science.abf6840.

  2. Hsia, Yang, et al. “Design of a Hyperstable 60-Subunit Protein Icosahedron.” Nature, vol. 535, no. 7610, 7610, Nature Publishing Group, July 2016, pp. 136–39., doi:10.1038/nature18010.

  3. Zakeri, Bijan, et al. “Peptide Tag Forming a Rapid Covalent Bond to a Protein, through Engineering a Bacterial Adhesin.” Proceedings of the National Academy of Sciences, vol. 109, no. 12, National Academy of Sciences, Mar. 2012, pp. E690–97., doi:10.1073/pnas.1115485109.

Last Fact Checked on May 20th, 2021.


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