New technology could protect against different variants of coronavirus

The SARS-CoV-2 virus that is at the origin of the COVID-19 pandemic is just one of many viruses in the coronavirus family.

Many of them circulate in populations of animals like bats and have the potential to “jump” into the human population, just like SARS-CoV-2. Researchers in the lab of Pamela Björkman, David Baltimore Professor of Biology and Bioengineering, are working on the development of vaccines for a wide range of related coronaviruses, with the aim of preventing future pandemics.

Now, led by graduate student Alex Cohen, a team from Caltech has engineered a nanoparticle of 60 protein-based subunits onto which pieces of up to eight different types of coronavirus have been attached.

When injected into mice, this vaccine induces the production of antibodies that react to a variety of different coronaviruses – including similar viruses that were not presented on the nanoparticle.

The research is described in an article in the journal Science.

This vaccine platform, called the mosaic nanoparticle, was initially developed by collaborators at the University of Oxford. The nanoparticle is shaped like a cage made up of 60 identical proteins, each of which has a small protein tag that functions like a piece of Velcro.

Cohen and his team took fragments of spike proteins from different coronaviruses (spike proteins play the biggest role in infection) and designed each to have a protein tag that would bind to those on the cage – l other half of the Velcro piece.

When these viral pieces were mixed with the structure of the nanoparticle cage, each virus tag stuck to a tag on the cage, resulting in a nanoparticle with spikes representing different strains of coronavirus on its surface.

Displaying eight different coronavirus tip fragments (known as receptor binding domains or RBDs) with this particle platform generated a diverse antibody response, which is an advantage over vaccination methods traditional ones that feature pieces of a single type of virus.

After inoculation, the antibodies subsequently produced by the mice were able to react to many different strains of coronavirus. Importantly, the antibodies were reactive to related strains of coronavirus that were not present on the nanoparticle.

This suggests that by presenting the immune system with several different coronavirus variants, the immune system learns to recognize common features of coronaviruses and could therefore potentially respond to a newly emerging coronavirus – not just a variant of SARS-CoV-2 – which could cause another pandemic.

While the team is still studying the mechanism underlying this phenomenon, the results are promising. The next step is to examine whether the immunization prevents viral infection and / or symptoms of infection in animals producing these antibodies.

If we can show that the immune response induced by our nanoparticle technology does indeed protect against disease resulting from infection, then we hope that we can advance this technology in human clinical trials, although many steps must be taken. ‘here there. so what.”

Alex Cohen, graduate student, California Institute of Technology

“We do not anticipate that this methodology will replace existing vaccines, but it is good to have many tools at hand in the face of future emerging viral threats.”

“Unfortunately, SARS-CoV-2 is unlikely to be the last coronavirus to cause a pandemic,” says Björkman. “Alex’s results show that it is possible to elevate various neutralizing antibody responses, even against strains of coronavirus that were not represented on the injected nanoparticle. We therefore hope that this technology can be used to protect against future animal coronaviruses that cross in humans. Additionally, nanoparticles elicit neutralizing responses against SARS-CoV-2, so it might be possible to use them now to protect against COVID-19 as well as other coronaviruses with pandemic potential. “