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The search for a universal vaccine against covid

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

To make their mosaic of nanoparticles, Cohen, Bjorkman and their collaborators chose proteins from the surfaces of 12 coronaviruses identified by other research groups and detailed in the scientific literature. These included 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 added a coronavirus found in a scaly anteater known as a pangolin. All the strains had already been genetically sequenced by other groups and share 68 to 95% of the same genomic material. Therefore, Cohen and Bjorkman could be relatively certain that at least some portions of each distinct spike protein they chose to put on the outside of their nanoparticle would 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 did three shots. One, for comparison purposes, had all 60 slots filled by particles taken from a single strain of SARS-CoV-2, the virus that causes covid-19. The other two were mosaics, each showing a mixture of protein fragments taken from eight of the 12 bat, human and pangolin coronavirus strains. The remaining four strains were not included in the vaccine so the researchers could test whether it would still protect against them.

In mouse studies, all three vaccines bound equally well to the covid-19 virus. But when Cohen sat down to see his results, he was surprised at how potently the mosaic nanoparticles behaved when exposed to different strains of coronavirus that were not represented in the spikes they had been exposed to.

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

New era

In recent months, Bjorkman, Cohen and their colleagues have been testing the vaccine in monkeys and rodents. So far it seems to be working. Some of the experiments moved slowly because they had to be carried out by collaborators abroad in special high-security biosafety labs designed to ensure highly contagious viruses don’t escape. But when the results finally appeared in Science, the paper received widespread attention.

Pamela Bjorkman

COURTESY OF CALTECH

Other promising efforts are moving in parallel. at the University of Washington Protein Design Institute, biochemist Neil King he has custom-designed hundreds of new types of nanoparticles, “sculpting them atom by atom,” he says, in such a way that the atoms assemble themselves, attracted to the correct positions by other pieces designed to carry complementary geometric and chemical charges. In 2019, King’s collaborator Barney Graham at NIH was the first to successfully show that mosaic nanoparticles could be effective against different strains of influenza. King, Graham and collaborators formed a company to modify and develop the technique, and have a nanoparticle influenza vaccine in Phase 1 clinical trials. They are now deploying the new technology against a range of different viruses, including SARS-CoV- two.

Despite recent promising developments, Bjorkman warns that his vaccine may not protect us from all coronaviruses. There are four families of coronaviruses, each one a little different from the next, and some target entirely different receptors on human cells. Therefore, there are fewer conserved sites among coronavirus families. His laboratory vaccine focuses on a universal vaccine for sarbecovirus, the subfamily that contains the SARS and SARS-coV-2 coronaviruses.

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