New mutation-mapping tool could yield stronger Covid boosters, universal vaccines

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Researchers have developed a novel platform which can quickly identify common immune-escape mutations in SARS-CoV-2, and suggest which antibodies are going to be effective against the circulating strains of the virus that causes COVID-19.

The research, published in the journal Cell Reports on Tuesday, may pave the way for universal vaccines for not only COVID-19, but also potentially for influenza, HIV and other deadly global viruses.

“We have developed a predictive tool that can tell you ahead of time which antibodies are going to be effective against circulating strains of virus,” said study lead author Timothy Whitehead, associate professor at the University of Colorado Boulder, US.

“But the implications for this technology are more profound: If you can predict what the variants will be in a given season, you could get vaccinated to match the sequence that will occur and short-circuit this seasonal variation, Whitehead noted.

The researchers developed a genetically modified version of baking yeast to express some of SARS-CoV-2’s viral spike proteins along its surface, with which they can map resulting mutations that form and escape neutralising antibodies.

The resulting roadmap could inform the development of more effective booster vaccines and tailored antibody treatments for patients with severe cases of COVID-19, Whitehead said.

Spike proteins, used by SARS-CoV-2 to enter and infect the human cells, are sharp bumps that stick out from the surface of viruses in the coronavirus family.

When antibodies recognise the spike proteins, latch on, and inhibit them from binding to cells, they prevent infection.

“There are mutations on the spike protein that prevent an antibody from going in and recognising it. Just like getting a new haircut, you look like a different person; this looks like a different virus to that antibody,” said Whitehead.

In the case of the more contagious Delta variant that was first identified in India, mutations on the spike proteins have made it more contagious and reduced the efficacy of some antibody therapies.

The researchers needed to identify mutations on the spike protein that could prevent antibodies from working.

Irene Francino-Urdaniz, a graduate student at the University of Colorado, developed a genetically engineered strain of common baker’s yeast, which could display different portions of the viral spike protein on its surface.

She then discovered how to screen through thousands of mutations in a single test tube to find the ones that evaded neutralising antibodies.

The researchers can see a wide variety of mutations develop at the same speed at which the yeast can grow, giving them an invaluable head start.

The team has already found some of the same mutations now circulating the globe, as well as identified more mutations with the potential to evade our immune systems.

They will also provide all their libraries of information, methods and software as an openly available community resource to accelerate new therapeutic strategies against SARS-CoV-2.

This means the next COVID-19 vaccine or booster shot produced for the public could have the ability to pack the most punch possible, according to the researchers.

It also gives hope for those who are immunocompromised or remain at a higher risk of contracting a bad case, as this research can be applied to proactively prepare antibody cocktails for specific mutations, giving them a better chance at survival and recovery.

The researchers said due to the adaptability of new mRNA vaccines which work with spike proteins, the applications of this research are not limited to one virus.

“You can use it for mapping trajectories for influenza and for HIV potentially; for other viral diseases that are known, and also potentially emerging pandemic ones,” Whitehead added.