In May 2024, researchers at the University of Cambridge stated that they have developed a new vaccine technology to provide protection against a “broad range of coronaviruses”, including “ones we don’t even know about”. The work came out of a collaboration between University of Cambridge, University of Oxford, and Caltech. The research, published in Nature Nanotechnology, explores the use of quartets of “linked” receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links: Quartet Nanocages. This nanomedicine approach could offer potential to “confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection”.
A new strategy
The authors comments that, although existing vaccination strategies have “shown success” in the reduction of death and serious illness from SARS-CoV-2, new strategies are “urgently needed”. Furthermore, future pandemic threats from coronaviruses will be important. Nanoscale organisation is a “key signal” for the programming of immune responses, with highly multivalent display of antigens on virus-like particles (VLPs) or other nanoparticles enhancing the strength and persistence of immune responses.
Recent work has displayed a “panel of protein variants” on the surface of VLPs to drive expansion of B cells recognising common features on various antigens. The approach has been tested in SARS-CoV-2, with mosaic nanoparticles displaying multiple RBDs from the Spike of different sarbecoviruses. In the latest study, the researchers establish the production of “multiviral Quartet Nanocages”, initially expressed from RBDs of four different viruses, concatenated as a single polypeptide chain.
The authors measured the antibody responses to the range of sarbecoviruses displayed on the Quartet Nanocage, to sarbecoviruses that were not present in the chain, and to SARS-CoV-2 variants of concern.
“The magnitude and breadth of antibody induction show that Quartet Nanocages may provide a scalable route to induce neutralising antibodies across a range of related viruses, to prepare for emerging outbreak disease threats.”
Protective promise
The University of Cambridge suggests that the Quartet Nanocage is a “ball of proteins held together by incredibly strong interactions”. To this, chains of viral antigens are attached with a “novel ‘protein superglue’”. In study, the new vaccine raised a “broad immune response”. As its design is “much simpler” than other broadly protective vaccines in development, researchers hope that it could proceed to clinical trials quickly.
This approach, proactive vaccinology, is where scientists develop a vaccine before the disease-causing pathogen has emerged. It is most effective when the vaccine targets specific regions that are shared in related coronaviruses. This vaccine, which doesn’t include the SARS-CoV-1 coronavirus behind the 2003 SARS outbreak, does induce an immune response to the virus.
Graduate student and first author, Rory Hills, suggests that the team is focused on creating a “vaccine that will protect us against the next coronavirus pandemic” and having it “ready before the pandemic has even started”.
“We’ve created a vaccine that provides protection against a broad range of different coronaviruses – including ones we don’t even know about yet.”
Professor Mark Howarth of the Department of Pharmacology states that “we know enough about coronaviruses, and different immune responses to them, that we can get going with building protective vaccines against unknown coronaviruses now”.
“Scientists did a great job in quickly producing an extremely effective COVID vaccine during the last pandemic, but the world still had a massive crisis with a huge number of deaths. We need to work out how we can do even better than that in the future, and a powerful component of that is starting to build the vaccines in advance.”
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