Scientists Develop Simple Vaccine With Potential to Stop Future Pandemics : ScienceAlert

The rapid development of vaccines that protect against COVID is a remarkable scientific achievement that has saved millions of lives. Vaccines have demonstrated substantial success in reducing death and severe illness after COVID infection.

Despite this success, the effects of the pandemic have been devastating, and it is essential to consider ways to protect against future pandemic threats.

Besides 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 cause future outbreaks.

My colleagues and I recently showed, in mice, that a single, relatively simple vaccine can protect against a range of coronaviruses, even those that have not yet been identified. This is a step toward our goal of what is called “proactive vaccinology,” where vaccines are developed against pandemic threats before they can infect humans.

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Conventional vaccines use a single antigen (part of a virus that triggers an immune response) that generally protects against that virus and that virus alone. They tend not to 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 increasing immune responses against different coronaviruses. These mosaic nanoparticles use a type of protein superglue technology that irreversibly connects two different proteins.

This “superglue” is used to decorate a single nanoparticle with multiple receptor-binding domains – a key part of a virus located on the spike protein – that come from different viruses. The vaccine focuses on a subgroup of coronaviruses called sarbecoviruses, which includes the viruses that cause COVID, SARS and several bat viruses that can infect humans.

As a virus evolves, some parts change while others stay the same. Our vaccine incorporates evolutionarily linked receptor binding domains (RBDs), so that a single vaccine trains the immune system to respond to parts of the virus that remain unchanged.

This protects against viruses represented in the vaccine and, importantly, also protects 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.

A simpler vaccine

In a collaboration between the universities of Oxford, Cambridge and Caltech, we have developed a simpler vaccine that still offers this broad protection. We achieved this by genetically fusing the RBDs of four different sarbecoviruses to form a single protein that we call a “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 sarbecoviruses not present in the vaccine. This shows the potential for protection against related viruses that may not have been discovered at the time the vaccine was produced.

Along with this streamlined production and assembly process, our new vaccine elicited immune responses in mice that at least matched, and in many cases exceeded, those elicited by our original mosaic nanoparticle vaccine.

Given the large portion of the world’s population vaccinated or previously infected with SARS-CoV-2, there was concern that an existing response to SARS-CoV-2 would limit the potential for protection against other coronaviruses. However, we have shown that our vaccine is capable of triggering a broad anti-sarbecovirus immune response, even in mice previously immunized against SARS-CoV-2.

Our next step is to test this vaccine in humans. We also apply this technology to protect against other groups of viruses that can infect humans.

All of this brings us closer to our vision of developing a library of vaccines against viruses with pandemic potential before they have a chance to spread in humans.

Rory Hills, PhD student, biochemistry, University of Oxford

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Gn Health

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