Tech

The hunt for a universal covid vaccine


The key to a universal vaccine is the nanoparticle mosaic with lots of different viral fragments clustered close together on its surface. The immune system’s B cells, which produce specific antibodies, have the ability to find and bind to at least some of these conserved viral fragments, which remain unchanged on new variants. As a result, B cells will produce antibodies that are effective against even previously unseen variants.

To create their mosaic nanoparticle, Cohen, Bjorkman and their colleagues selected proteins from the surface of 12 coronaviruses identified and detailed in the scientific literature by other research groups. These include the virus that caused the first SARS outbreak and the virus that caused covid-19, but also a non-human virus found in bats in China, Bulgaria and Kenya. For good measure, they also threw in a coronavirus found in a species of scaly anteater known as a pangolin. All strains have been genetically sequenced by other groups and share 68 to 95% of the same genetic material. Thus, Cohen and Bjorkman can be relatively certain that at least some part of each distinct mutant protein they choose to place outside their nanoparticle will be shared by some other virus.

The key to a universal vaccine is the nanoparticle mosaic with lots of different viral fragments clustered close together on its surface.

Then they created three vaccines. One, for comparison purposes, has all 60 slots occupied by particles taken from a strain of SARS-CoV-2, the virus that causes covid-19. The other two are mosaics, each showing a mixture of protein fragments taken from eight of the 12 strains of bat, human and pangolin coronaviruses. The remaining four strains did not receive the vaccine so the researchers could test to see if it protected them.

In mouse studies, all three vaccines bind equally well to the covid-19 virus. But when Cohen sat down to see his results, he was shocked to see how much stronger the mosaic nanoparticles were when exposed to different strains of coronavirus that weren’t present on the spikes they were exposed to.

The vaccine triggered the production of an army of antibodies that attack the parts of the protein that are the least changed among the different coronavirus strains — in other words, the parts are conserved.

New era

In recent months, Bjorkman, Cohen and their colleagues have tested the vaccine on monkeys as well as rodents. So far seems to be working. Some tests are slow because they must be performed by collaborators abroad in special high-security biosecurity laboratories designed to ensure that viruses are highly infectious does not escape. But when the results finally appeared in Science, the paper received widespread attention.

Pamela Bjorkman
Pamela Bjorkman

CALTECH’S COURSE

Other promising efforts are underway in parallel. At the University of Washington’s 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 self-assemble, attracted to precise positions by other engineered pieces. to carry free geometric and chemical charges. In 2019, King collaborator Barney Graham at NIH was the first to successfully demonstrate that mosaic nanoparticles can be effective against different strains of influenza. King, Graham and collaborators have formed a company to modify and develop this technique, and they have a nanoparticle flu vaccine in phase 1 clinical trials. They are now deploying new technology against various viruses, including SARS-CoV-2.

Despite recent promising developments, Bjorkman warns that her vaccine probably won’t protect us from all coronaviruses. There are four families of coronaviruses, each slightly different from the next, and some that target completely different receptors in human cells. Therefore, there are fewer conserved sites in the coronavirus families. The vaccine from her lab focuses on a common vaccine for the sarbecovirus, a subfamily that contains the SARS and SARS-coV-2 coronaviruses.



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