The SARS-CoV-2 virus that causes COVID-19 pandemic is just one of many different viruses in the coronavirus family.
Many of these circulate in animal populations such as bats and have the ability to “jump” into the human population, just as SARS-CoV-2 did. Researchers in the laboratory of Pamela Björkman, David Baltimore Professor of Biology and Bioengineering, are working on developing vaccines for a wide range of related coronaviruses, with the goal of preventing future pandemics.
Now, led by graduate student Alex Cohen, the Caltech team has designed a protein-based 60-subunit nanoparticle on which fragments of up to eight different types of coronavirus have been linked.
When ingested into mice, this vaccine induces the production of antibodies that respond to a combination of different coronaviruses – including similar viruses that have not been passed on the nanoparticle.
The research is described in a paper in the journal Science.
This vaccine platform, called mosaic nanoparticle, was first developed by colleagues at Oxford University. The cage-shaped nanoparticle is made up of 60 identical proteins, each of which has a small protein tag that acts as a piece of Velcro.
Cohen and his team took fragments of the spike proteins of various coronaviruses (spike proteins play the major role in infection) and each invented to attach a protein tag to those on the cage – half another piece of Velcro.
When these viral fragments were mixed together with a nanoparticle cage structure, each virus tag was stuck to a tag on the cage, resulting in a nanoparticle exhibiting spikes representing different types of coronavirus on its surface.
By exposing eight different coronavirus spike fragments (known as receptor binding domains or RBDs) with this granular platform resulted in a diverse response of antibody, which is an advantage over traditional vaccination methods that show pieces from just one type of virus.
After inoculation, the mice-derived antibodies were able to respond to a wide variety of coronavirus types. Importantly, the antibodies were reactive to associated strains of coronavirus that were not present on the nanoparticle.
This suggests that, by presenting the immune system with a number of different coronavirus modifications, the immune system learns to recognize the common features of coronaviruses and thus may respond to a developing coronavirus. re-emergence – not just a SARS-CoV-2 variable – that could cause another pandemic.
While the team is still examining the equipment that underlies this phenomenon, the results are promising. The next step is to examine whether vaccination prevents viral infection and / or signs of infection in animals that produce these antibodies.
If we can show that the immune response resulting from our nanoparticle technology actually protects against the onset of disease, we hope that we could advance this technology to human clinical trials, although there are many steps that need to be taken between now and then. “
Alex Cohen, Studdent Graduate, California Institute of Technology
“We don’t expect this approach to replace existing vaccines, but it’s good that there will be a lot of tools when viral threats emerge in the future.”
“Unfortunately SARS-CoV-2 is unlikely to be the last coronavirus to cause pandemic,” says Björkman. “Alex ‘s results show that it is possible to elicit a variety of neutral responses, even against coronavirus rays that were not represented on the introduced nanoparticle. So we hope that use this technology to protect against future animal coronaviruses that enter humans.In addition, the nanoparticles have neutral responses against SARS-CoV-2, and as so it may be possible to use them now to protect against COVID-19 as well as other pandemic-capable coronaviruses. “
Source:
California Institute of Technology
Magazine Reference:
Cohen, AA, et al. (2021) Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice. Science. doi.org/10.1126/science.abf6840.