At a time when the question of a third dose of vaccine for all is on the table, research using an atomic force microscope has revealed more stable—and therefore more difficult to break—bindings of SARS-CoV-2 variants to receptors in our cells. Combined with the loss of affinity of some antibodies for variant spike proteins, these results beg the question of adapting the vaccine to the variants rather than administering a third dose of existing vaccines.
This was observed at UCLouvain using the atomic force microscope, state-of-the-art equipment for studying, among other things, the bonds between viruses and living cells. The variants, notably the Kappa variant, a close cousin of Delta, adopt a new strategy to bind more effectively to the cells they want to invade. Rather than increasing the strength of their binding to a specific location on our ACE2 receptors—the coronavirus’s main entry point into our cells—they multiply small bindings over a larger area. As a result, the “overall” bond of the variant to cells is more stable. “From an evolutionary point of view, this is a strategy that makes sense since these viruses are subject to numerous fluxes at the level of the respiratory epithelium, the tissue that covers the surface of the respiratory tract,” explains David Alsteens, an FNRS research associate and WELBIO investigator at the Louvain Institute of Biomolecular Science and Technology, who led this research published in Nature Communications.
From Alpha to Kappa: from press stud to Velcro
It’s almost as if the original SARS-CoV-2 strain binds to our cells with a press stud while the variants have opted for a Velcro system whose each tiny binding isn’t as strong as the press stud but whose tiny bindings collectively create a very stable interaction between the variants and our cells. “We worked with different variants including Kappa, which, at the time of the trials for this research, was the new variant from India. We can assume that the Delta variant behaves in a very similar way.”
David Alsteens’s team also tested the affinity and binding of the two types of antibody produced when exposed to the original virus strain or a vaccine. Of these two antibodies, one was still able to block the Kappa variant’s spike protein from binding to the ACE2 receptor, while the other had no effect it.
Modify vaccines?
This research has made it possible to visualise and measure in concrete terms how mutations change the interactions between the virus and our cells. It also introduces a question that doesn’t seem to be on the table at the moment: What about adapting vaccines to new variants? When vaccines, especially mRNA vaccines, were first introduced, pharmaceutical companies claimed that one of their great advantages was that they could be easily adapted to remain effective against new variants. A time frame of six weeks for a suitable vaccine was suggested. As the Delta variant has been circulating for several months and the question of a third dose of vaccine for all was decided at the Belgian government’s 17 November Codeco meeting, the answer to this question could be of interest to many (see interview with Sophie Lucas).
To learn more about David Alsteens’s team research on coronavirus:
Video with David Alsteens and related article posted 2 April 2020:
- https://www.youtube.com/watch?v=iNh3b0Cln4I (French)
- https://uclouvain.be/en/sciencetoday/news/lock-the-door-on-coronavirus.html
To learn more about David Alsteens’s research:
Video on David Alsteens’s research (English):
Articles:
- https://uclouvain.be/en/sciencetoday/news/les-reovirus-des-armes-contre-le-cancer-thinsp.html (November 2018)
- https://uclouvain.be/en/sciencetoday/news/scruter-les-mecanismes-moleculaires-pour-mieux-cibler-les-traitements.html (January 2016)
“Visages de la recherche” video (French):