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Covid vaccines - how can immune imprinting help experts to rethink jabs?

Article for the FT by Clive Cookson and Ian Bott in London and Jamie Smyth in New York – 03.07.22

More than two years into the pandemic, people have acquired different levels of immunity through infections and shots

A surge in Covid-19 hospital admissions driven by the BA.5 subvariant of Omicron, accompanied by the inability of vaccines to prevent reinfection, has prompted health policymakers to rethink their approach to boosters.

US regulators last week recommended changing the design of vaccines to produce a new booster targeting Omicron — the first change to the make-up of shots since their introduction in late 2020. Research into immune imprinting, whereby exposure to the virus via either infection or vaccination determines an individual’s level of protection, is now driving the debate over the make-up of Covid-19 vaccines.

Immunologists say that, more than two years into the coronavirus pandemic, people have acquired very different types of immunity to the Sars-Cov-2 virus, depending on which strain or combination of strains they have been exposed to — leading to big differences in Covid-19 outcomes between individuals and countries.

“The effect is more nuanced than ‘more times you have it, less protection you get’,” said professor Danny Altmann of Imperial College London, who is investigating the phenomenon with colleagues. “It’s more helpful to consider it as progressive fine-tuning of a huge repertoire. Sometimes this will be beneficial for the next wave, sometimes not.”

What is immune imprinting?

After someone encounters a virus for the first time, through infection or vaccination, the immune system remembers its initial response in a way that usually weakens the response to future variants of the same pathogen but may sometimes strengthen it. Proteins on the “spike”, which the virus uses to bind with human cells, play a key role.

“Our first encounter with the spike antigen, either through infection or vaccination, shapes our subsequent pattern of immunity through immune imprinting,” said Professor Rosemary Boyton of Imperial College.

The pattern has been observed for many years in flu and dengue virus, when it was usually called original antigenic sin. Studies are now demonstrating that it applies to Sars-Cov-2 too, although the effects are hard to pin down, according to Altmann, who prefers the term “immune imprinting” to the biblical connotations of original sin.

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Diagram showing how populations develop different immune responses over the course of a pandemic

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