Predicting viral evolution may let vaccines be prepared in advance

New techniques could programme people’s immune systems against future pathogens | Science & technology

8/6/2021 4:19:00 AM

Understanding what a virus might look like in years to come gives those designing vaccines and therapies a leg up, enabling them to prime more immune systems sooner, so that fewer people die

New techniques could programme people’s immune systems against future pathogens | Science & technology

.Like immune responses themselves, however, vaccination generally has to wait for the appearance of the pathogen in question before it can do its stuff. There is therefore a delay between a pathogen’s arrival on the scene and the deployment of a vaccine against it. That delay costs lives. Even in the case of covid-19, which has prompted the fastest vaccine-development programme the world has ever witnessed, millions are reckoned to have died by the time vaccinations began to be given in the rich world at the end of 2020.

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But, just as vaccination introduces immune systems to pathogens that are remote from them in space, new techniques which have come to the fore during the current pandemic offer the possibility of introducing them to pathogens that are remote from them in time—pathogens, indeed, that have not yet evolved, but which are likely to do so in the future. Thanks to a combination of high-throughput

DNA-sequencing technologies and modern machine-learning it is now possible not merely to observe which variants of a virus are circulating, but also to suggest how they are likely to change. Understanding in this way what a virus might look like in the months and years to come gives those designing vaccines and therapies a leg up, enabling them to prime more immune systems sooner, so that fewer people die.

The starting point for these predictions is the sort of work going on in the laboratory of Jesse Bloom, a virologist at the Fred Hutchinson Cancer Research Centre, in Seattle. Dr Bloom and his colleagues grow variants of coronavirus spike protein (the molecule which such viruses use to attach themselves to cells they are about to infect) in Petri dishes. They then scan through these to discern which mutations have what effects.

They have named this technique deep mutational scanning. It uses an array of yeast cells that have been genetically modified to express a part of the spike protein called the receptor-binding domain (RBD). As the yeast cells churn out theirRBDs, many emerge, thanks to errors inherent in their production, with slight deviations in their structures from that of the original wild-type virus. Dr Bloom’s team then test the

RBDs from each yeast cell to see how tightly they bind toACE2, a receptor protein found on the surfaces of some human cells, to which the coronavirus attaches itself before entering those cells.RBDs that bind tightly have their underlying genomes sequenced, to determine which mutations are present.

When Dr Bloom’s team ran this scan in the summer of 2020, on spike from a version of the virus then circulating, they spotted a mutation calledN501Ywhich appeared to confer a binding advantage. A few months later, that mutation appeared in the Alpha variant, which for several months was dominant across much of the world. Dr Bloom says it would be “charitable” to say that he and his colleagues had predicted the emergence of

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N501Y. It was by no means the only mutation of interest to turn up. But even so, having a limited set of such mutations to focus on is useful for narrowing the field of research.Getting the message acrossOne firm taking advantage of that narrowing is Flagship Labs 77, a company based in Boston that has until recently been working in secret.

FL77, as it is known for short, is a spin out from Flagship Pioneering, a biotechnology incubator run by Noubar Afeyan, a venture capitalist. Moderna, a trailblazer of the messenger-RNA-based technology that helped speed up the production of coronavirus vaccines, was also a Flagship Pioneering company, and Mr Afeyan is its chairman.

FL77’s researchers are trying to combine experimental data of the sort Dr Bloom is collecting with computation, in order to predict how viruses may evolve. That information could be used to develop vaccines and therapeutic antibodies pre-emptively. Whereas Dr Bloom’s laboratory predicts only single mutational hops,

FL77can currently manage five or six. The firm calls its system “Global Pathogen Shield”. The details remain confidential, but in June it published a paper outlining the project’s goals. This described the scale of the challenge involved in keeping pace with viral evolution—namely that biology is so diverse that even looking at a small slice of possible mutations leads to a problem which rapidly grows beyond the plausible limits of observation, to one on the scale of counting and categorising all of the atoms of which Earth is composed.

The conventional response to such overwhelming odds has been observation rather than experimentation. The World Health Organisation’s Global Influenza Surveillance and Response System does this for flu. It monitors which viruses are circulating in the southern hemisphere when it is winter there, in order to focus attention on which strains will be relevant during the next northern-hemisphere winter, and vice versa. During the coronavirus pandemic, organisations such as Nextstrain and

GISAIDhave kept track of variants of Read more: The Economist »

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Wondering what’s the cost to keep the manpower and technology for deep mutational scanning on predictions. Why not directly tackle the issue of wildlife trade, deforestation, climate change and overpopulation for the emerging of zoonotic diseases. But first, we need to figure out whether people dying is a good thing or not , to the earth ,the whole creature environment.

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