The key to a universal vaccine is a mosaic nanoparticle with so many different viral fragments clustered in close proximity on its surface. B cells of the immune system, which make specific antibodies, are likely to find and bind to at least some of these conserved parts of the virus, which remain unchanged on the new variants. Thus, B cells will make antibodies effective against even previously invisible variants.
To make their mosaic nanoparticle, Cohen, Bjorkman and their collaborators selected proteins from the surfaces of 12 coronaviruses that had been identified by other research groups and described in detail in the scientific literature. Among them are the viruses that caused the first SARS epidemic and the one that causes covid-19, as well as non-human viruses found in bats in China, Bulgaria and Kenya. For good measure, they threw in a coronavirus found in a scaly anteater known as a pangolin. All strains have already been genetically sequenced by other groups and share 68 to 95% of the same genomic material. Thus, Cohen and Bjorkman could be relatively certain that at least some parts of each different protein spike they chose to place on the outside of their nanoparticle would be shared by some of the other viruses.
Then they made three vaccines. One, by comparison, had all 60 sites occupied by particles taken from a single strain of SARS-CoV-2, the virus that causes covid-19. The other two were mosaics, each displaying a mixture of protein fragments taken from eight of 12 bat, human and pangolin coronavirus strains. The remaining four strains were left out of the vaccine so 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 look at his results, he was shocked at how much more potent the mosaic nanoparticles worked when they were exposed to different strains of the coronavirus that weren’t represented on the spikes they were exposed to.
The vaccine triggered the production of armies of antibodies to attack the parts of the protein that have changed the least among different strains of the coronavirus – in other words, the parts that have been conserved.
A new era
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 of the experiments proceeded slowly because they had to be carried out by overseas collaborators in special high-security biosafety laboratories designed to ensure that the highly contagious viruses did not escape. But when the results finally appeared in Science, the work received widespread attention.
Other promising efforts run parallel. At the University of Washington Institute for Protein Design, biochemist Neil King has specially designed hundreds of new types of nanoparticles, “assembling them atom by atom,” he says, in such a way that the atoms assemble themselves, pulled into the correct position by other parts designed to carry complementary geometric and chemical charges. In 2019, King’s collaborator Barney Graham of the NIH was the first to successfully demonstrate that mosaic nanoparticles can be effective against different strains of influenza. King, Graham and colleagues have founded a company to modify and develop the technique, and have a nanoparticle flu vaccine in phase 1 clinical trials. They are now applying new technology against various viruses, including SARS-CoV-2.
Despite recent promising developments, Bjorkman warns that her vaccine is unlikely to protect us from all coronaviruses. There are four families of coronaviruses, each slightly different from the other, and some targeting completely different receptors in human cells. Thus, there are fewer conserved sites in the coronavirus families. The vaccine from her lab focuses on a universal vaccine for sarbecovirus, a subfamily that includes SARS coronaviruses and SARS-CoV-2.