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The rapid development of COVID-19 vaccines was a remarkable scientific achievement that saved millions of lives. Vaccines have demonstrated substantial success in reducing death and severe disease following Covid infection. Despite this success, the effects of the pandemic have been devastating, and it is important to consider how to avoid the risks of future pandemics. Along with SARS-CoV-2 (the virus that causes COVID), previously unknown coronaviruses have been responsible for the deadly outbreaks of SARS (2003) and MERS (2012 outbreak with ongoing cases).
Meanwhile, several circulating bat coronaviruses have been identified as having the potential to infect humans – which could lead to future outbreaks. My colleagues and I recently showed in mice that a single, relatively simple vaccine can protect against many types of coronaviruses – even those that have not yet been identified. This is a step toward our goal of what is known as “proactive vaccinology,” where vaccines are developed against pandemic threats before they infect humans.
Traditional vaccines use a single antigen (the part of the virus that triggers an immune response) that typically protects against that virus and that virus alone. They do not protect against various known viruses, or viruses that have not yet been discovered. In previous research, we have shown the success of “mosaic nanoparticles” in enhancing immune responses to various coronaviruses. These mosaic nanoparticles use a type of protein superglue technology that irreversibly links two different proteins together.
This “superglue” is used to decorate a single nanoparticle with multiple receptor-binding domains – a major part of the virus located on the spike protein – that come from different viruses. The vaccine focuses on a sub-group of coronaviruses called sarbecoviruses, which includes the viruses that cause COVID, SARS, and several bat viruses that have the potential to infect humans.
As a virus evolves, some parts of it change while other parts remain the same. Our vaccine incorporates evolutionarily related receptor-binding domains (RBDs), so a single vaccine trains the immune system to respond to parts of the virus that remain unchanged. It protects against viruses that are included in the vaccine and, critically, also against related viruses that are not included in the vaccine. Despite this success with mosaic nanoparticles, the vaccine was complex, making it difficult to produce on a large scale.
simple vaccine
In collaboration between the universities of Oxford, Cambridge and Caltech, we have now developed a simpler vaccine that still provides this broad protection. We genetically combined the RBDs from four different sarbecoviruses to create a protein we call the “quartet.” We then use a type of protein glue to attach these quartets to a “protein nanocage” to make the vaccine.
When mice were immunized with these nanocage vaccines, they produced antibodies that neutralized a range of sarbecoviruses, including ones not present in the vaccine. This reflects the ability to protect against related viruses that were not discovered at the time the vaccine was produced. With this streamlined production and assembly process, our new vaccine generated immune responses in mice that at least matched, and in many cases exceeded, those elicited by our original mosaic nanoparticle vaccine.
Given that much of the world has been vaccinated against or has already been infected with SARS-CoV-2, there was concern that the current response to SARS-CoV-2 would limit the ability to protect against other coronaviruses. . However, we have shown that our vaccine is capable of mounting a broad anti-sarbecovirus immune response even in mice that were previously immunized against SARS-CoV-2.
Our next step is to test this vaccine in humans. We are also applying this technology to protect against other groups of viruses that can infect humans. All this brings us closer to our vision of developing a library of vaccines against viruses with pandemic potential before they have a chance to enter humans.
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