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Our new vaccine could protect against coronaviruses that haven't even
emerged yet - new study
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The rapid development of vaccines that protect against COVID was a
remarkable scientific achievement that saved millions of lives. The
vaccines have demonstrated substantial success in reducing death and
serious illness after COVID infection.
Despite this success, the effects of the pandemic have been
devastating, and it is critical to consider how to protect against
future pandemic threats. As well as 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 have recently shown, in mice, that a single,
relatively simple vaccine can protect against a range of coronaviruses
- even ones that are yet to be identified. This is a step towards our
goal of what is known as "proactive vaccinology", where vaccines are
developed against pandemic threats before they can infect humans.
Interview with the author, Rory Hills.
Conventional vaccines use a single antigen (part of a virus that
triggers an immune response) that typically protects against that
virus and that virus alone. They tend not to protect against diverse
known viruses, or viruses that have not yet been discovered.
In previous research, we have shown the success of "mosaic
nanoparticles" at raising immune responses to different 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 key part of a virus located on
the spike protein - that come from different viruses. The vaccine is
focused on a sub-group of coronaviruses called sarbecoviruses that
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 the parts of the virus that remain unchanged. This
protects against the viruses that are represented in the vaccine and,
critically, 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.
## Simpler vaccine
In a collaboration between the universities of Oxford, Cambridge and
Caltech, we have now developed a simpler vaccine that still provides
this broad protection. We achieved this by genetically fusing RBDs
from 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 immunised with these nanocage vaccines, they produced
antibodies that neutralised a range of sarbecoviruses, including
sarbecoviruses not present in the vaccine. This show the potential to
protect against related viruses that may not have been discovered at
the time that 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 raised by our original mosaic
nanoparticles vaccine.
Given the large fraction of the world vaccinated or previously
infected with SARS-CoV-2, there was a worry that an existing response
to SARS-CoV-2 would limit the potential to protect against other
coronaviruses. However, we have shown that our vaccine is able to
raise a broad anti-sarbecovirus immune response even in mice that had
previously been immunised 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 of this brings us closer to our vision of
developing a library of vaccines against viruses with pandemic
potential before they have had the opportunity to cross over into
humans.
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