News Desk :
Generally, immune systems mount responses only against pathogens that have already infected the bodies they are protecting. Science, though, can shorten the path to immunity by vaccination. This involves presenting the immune system with harmless or lookalike versions of dangerous pathogens so that it may create antibodies and killer cells hostile to the real thing in advance of any actual infection, thereby reducing its danger, said an article published in the Economist recently.
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.
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.
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.
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, FL77 can currently manage five or six. The firm calls its system “Global Pathogen Shield”. The details remain confidential.
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.
FL77 aims to take this much further-not only tracking which variants of a virus are where, but also predicting how they will evolve. It does this by feeding into a piece of software called Octavia data from a scaled-up version of Dr Bloom’s deep mutational scanning that runs assays on between 1m and 10m variants.
In covid-19 vaccines, the protein in question is spike. Updating vaccines to take account of predicted variants of spike is merely a matter of inserting the relevant genetic code at the start of the manufacturing process. At the least, such predictions would permit a library of candidate vaccines to be held ready, in anticipation of rapid manufacturing. At its most ambitious, FL77 imagines vaccinating people against variants of a pathogen that are not yet circulating, but are likely to.
Deep mutational scanning may have other uses, too. Gabriel Victora, an immunologist at Rockefeller University in New York, thinks predicting the evolution of a pathogen in this way will be useful not just for designing antibodies and vaccines, but also for detecting parts of the virus which change only rarely, and aiming antibodies at what would thus be reliable targets.
Seasonal flu vaccines already grapple with this problem when updating immune systems with information about the strain predicted to be circulating in the coming winter. Even after vaccination, immune systems may tend to make antibodies against the old virus instead. It is not clear whether the same thing will happen with updated messenger-RNA vaccines.
No programme will ever be able to predict the evolution of the entire array of pathogens which can plausibly infect human beings. But for those already known to pose a threat, systems like Octavia may be able to see far enough into the future to offer benefits.
FL77 is already doing this. The most radical version of the firm’s vision-vaccinating against variants and strains of pathogens that are yet to emerge-is some way off, if it ever happens. Protecting people by programming their immune systems against future pathogens, not just those already circulating, would be a fundamental shift in the meaning, purpose and ethics of vaccination. But even in the absence of that, pathogen prediction should soon serve to speed existing sorts of vaccination programmes. And every increase in the speed of vaccine development means thousands of saved lives, the article added.
