The key to the universal vaccine is the mosaic nanoparticle with so many different viral fragments clustered very close to its surface. It is likely that the immune system’s B cells, which generate specific antibodies, find and bind to at least some of these conserved pieces of the virus, which remain unchanged in the new variants. Thus, B cells will make antibodies effective even against previously unseen variants.
To make their mosaic nanoparticle, 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 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 released a coronavirus found in a scaly anteater known as a pangolin. All strains had already been genetically sequenced by other groups and share between 68 and 95% of the same genomic material. So Cohen and Bjorkman could be relatively certain that at least some portions of each different spike protein they chose to place 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 very close to its surface.
Then they did three vaccinations. One, for comparison, 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 showing a mix of protein fragments 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 them anyway.
In studies with mice, all three vaccines bound the covid-19 virus equally well. But when Cohen sat down to see his results, he was surprised at how much stronger the mosaic nanoparticles were when exposed to different strains of coronavirus 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 different strains of the coronavirus — the parts that are conserved.
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In recent months, Bjorkman, Cohen and their collaborators have been testing the vaccine in monkeys and rodents. So far, it seems to be working. Some of the experiments proceeded slowly because they had to be carried out by foreign collaborators in special high-security biosecurity laboratories designed to ensure that the highly contagious viruses did not escape. But when the results finally appeared in Science, the paper received widespread attention.
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Other promising efforts are moving in parallel. At the Institute for Protein Design at the University of Washington, biochemist Neil King has custom-designed hundreds of new types of nanoparticles, “sculpting them atom by atom,” he says, so that the atoms resemble themselves themselves, attracted by what is right. positions of other parts designed to carry complementary geometric and chemical loads. In 2019, King’s collaborator Barney Graham at the NIH was the first to successfully demonstrate that mosaic nanoparticles could be effective against different strains of influenza. King, Graham and colleagues formed a company to modify and develop the technique, and 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 recent promising developments, Bjorkman warns that his vaccine probably won’t protect us from all coronaviruses. There are four families of coronaviruses, each slightly different from the other, and some target completely different receptors on human cells. Thus, there are fewer conserved sites among coronavirus families. His lab’s vaccine focuses on a universal vaccine for sarbecovirus, the subfamily that contains SARS and SARS-CoV-2 coronaviruses.
