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The hunt for a universal covid vaccine


The key to the universal vaccine is the mosaic nanoparticle with many different viral fragments clustered closely together on its surface. B cells of the immune system that produce specific antibodies are likely to find and bind to at least some of these conserved virus fragments that remain unchanged in the new variants. Thus, B cells will make antibodies effective even against previously unseen variants.

To make the mosaic nanoparticles, Cohen, Bjorkman and their collaborators selected proteins from the surface of 12 coronaviruses described by other research groups and detailed in the scientific literature. These included the viruses that caused the first SARS outbreak and caused covid-19, as well as non-human viruses found in bats in China, Bulgaria and Kenya. As a good precaution, they also threw out a coronavirus found in a scaly anteater known as the pangolin. All strains had already been genetically sequenced by other groups and shared 68 to 95% of the same genomic material. Therefore, Cohen and Bjorkman can be relatively confident that at least some parts of each different spike protein they choose to embed outside their nanoparticles will be shared by some of the other viruses.

The key to the universal vaccine is the mosaic nanoparticle with many different viral fragments clustered closely together on its surface.

Then they made three vaccines. In one for comparison purposes, all 60 slots were occupied by particles from a single strain of SARS-CoV-2 that causes covid-19. The other two were mosaic, each showing a mix of protein fragments from eight of the 12 bat, human, and pangolin coronavirus strains. The remaining four strains were excluded from the vaccine so the researchers could test whether the vaccine would still protect against them.

In mouse studies, all three vaccines linked equally well to the covid-19 virus. But when Cohen sat down to look at their results, he was shocked at how strongly the mosaic nanoparticles performed when exposed to different strains of coronavirus that were not represented in the spikes they were exposed to.

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

New Age

In recent months, Bjorkman, Cohen and their collaborators have been testing the vaccine in monkeys as well as rodents. So far, it seems to be working. Some experiments progressed slowly because they had to be done by overseas collaborators in specialized high-security biosecurity labs designed to ensure highly infectious viruses could not escape. But when the results finally appeared in the journal Science, the paper received widespread attention.

Pamela Bjorkman
Pamela Bjorkman

PERMISSION OF CALTECH

Other promising efforts are running in parallel. at the University of Washington Institute of Protein Design, biochemist Neil King He says he has custom-designed hundreds of new kinds of nanoparticles by “shaping them atom by atom,” such that atoms will self-assemble and be pulled into the right positions by other parts designed to carry complementary geometric and chemical charges. In 2019, King’s collaborator at the NIH, Barney Graham, was the first to successfully demonstrate that mosaic nanoparticles can be effective against different strains of flu. King, Graham and collaborators formed a company to modify and improve the technique, and there is a nanoparticle flu vaccine in phase 1 clinical trials. They are now using the new technology against a variety of different viruses, including SARS-CoV-2.

Despite recent promising developments, Bjorkman says his vaccine will likely not protect us from all coronaviruses. There are four families of coronavirus, each slightly different from the other, and some target completely different receptors in human cells. Thus, there are fewer sites protected in coronavirus families. The vaccine in his lab focuses on a universal vaccine for sarbecovirus, the subfamily that includes SARS coronaviruses and SARS-coV-2.



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