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. Thus, the B cells will make antibodies effective against even 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 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 threw in 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. Thus, Cohen and Bjorkman could be relatively sure that at least some portions of each distinct spike protein they chose to place on the exterior 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 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 one displaying a mix of protein fragments taken from eight of the 12 bat, human, and pangolin coronavirus strains. The remaining four strains were left off the vaccine so the researchers could test whether it would protect against them 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 at how much more powerfully the mosaic nanoparticles performed when exposed to different strains of coronavirus not represented on 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 least among the different strains of coronavirus—the parts, in other words, that are conserved.
New era
In recent months, Bjorkman, Cohen, and their collaborators have been testing out 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 done by overseas collaborators in special high-security biosafety labs designed to ensure that highly contagious viruses do not 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’s Institute of Protein Design, biochemist Neil King has custom-designed hundreds of new types of nanoparticles, “sculpting them atom by atom,” he says, in such a way that the atoms self-assemble, attracted to the correct positions by other pieces engineered 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 could be effective against different flu strains. King, Graham, and collaborators formed a company to modify and develop the technique, and they have a nanoparticle influenza 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 likely won’t protect us from all coronaviruses. There are four families of coronaviruses, each a little different from the next, and some target entirely 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 contains SARS coronaviruses and SARS-coV-2.