October 2, 2022

The search for a universal covid vaccine

The search for a universal covid vaccine


The key to the universal vaccine is the mosaic nanoparticle with so many different viral fragments clustered in close proximity on its surface. The immune system’s B cells, which generate specific antibodies, are likely to find and bind to at least some of these conserved pieces of the virus, which remain unchanged on new variants. The B cells will therefore make antibodies effective against even previously unseen variants.

To make their mosaic nanoparticle, Cohen, Bjorkman and their collaborators selected proteins from the surfaces of 12 coronaviruses identified by other research groups and detailed in the scientific literature. These include the viruses that caused the first SARS outbreak and the one that causes covid-19, but also non-human viruses found in bats in China, Bulgaria and Kenya. For good measure, they also threw in a coronavirus found in a scaly anteater known as a pangolin. All the strains have already been genetically ordered by other groups and share 68 to 95% of the same genomic material. So Cohen and Bjorkman can be relatively certain that at least some portions of each distinct spike protein they chose to put on the outside of their nanoparticle will be shared by some of the other viruses.

The key to the universal vaccine is the mosaic nanoparticle with so many different viral fragments clustered in close proximity on its surface.

Then they made three vaccines. One, for comparison purposes, had all 60 slots occupied by particles taken from a single strain of SARS-CoV-2, the virus that causes covid-19. The other two were mosaics, each containing a mixture of protein fragments taken from eight of the 12 bat, human and pangolin coronavirus strains. The remaining four strains were left out of the vaccine so the researchers could test whether it would protect against it anyway.

In mouse studies, all three vaccines bound equally well to the covid-19 virus. But when Cohen sat down to look at his results, he was shocked by how much more potent the mosaic nanoparticles performed when exposed to different coronavirus strains not represented on the spikes they were exposed to.

The vaccine triggered the production of armies of antibodies to attack the parts of the proteins that have changed the least among the different coronavirus strains – the parts, in other words, that remain conserved.

New era

In recent months, Bjorkman, Cohen and their collaborators have tested the vaccine in monkeys as well as rodents. So far it seems to be working. Some of the experiments were slow because they had to be done by overseas collaborators in special high-security biosafety laboratories designed to ensure that highly contagious viruses did not escape. But when the results finally appeared in Science, the paper gained widespread attention.

Pamela Bjorkman
Pamela Bjorkman

COURTESY OF CALTECH

Other promising efforts are moving in parallel. At the University of Washington’s Institute for Protein Design, biochemist Neil King has custom-engineered hundreds of new types of nanoparticles, “shaping them atom by atom,” he says, in such a way that the atoms assemble themselves, attracted to the right positions by other pieces designed to carry complimentary geometric and chemical charges. In 2019, King’s collaborator Barney Graham at NIH was the first to successfully demonstrate that mosaic nanoparticles can be effective against different strains of influenza. King, Graham and collaborators founded a company to modify and develop the technique, and they have a nanoparticle flu vaccine in phase 1 clinical trials. They are now deploying the new technology against a variety of different viruses, including SARS-CoV-2.

Despite the recent promising developments, Bjorkman warns that her vaccine is unlikely to protect us against all coronaviruses. There are four families of coronaviruses, each a little different from the next, and some target completely different receptors in human cells. Thus, there are fewer sites conserved across coronavirus families. The vaccine from her lab focuses on a universal vaccine for the sarbecovirus, the subfamily that includes SARS-coronaviruses and SARS-coV-2.



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