The immune system responds more strongly to the strain of a virus that it first met, weakening response to other strains. Can this ‘imprinting’ be overcome?

By Rachel Brazil

During the summer of 2022, with the Omicron coronavirus variant running rampant, friends and relatives of immunologist Bob Seder kept asking him if they should postpone their COVID-19 boosters and wait for the new Omicron-tailored vaccine to become available. He told them not to delay.

Seder, acting chief of the Vaccine Immunology Program at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, suspected that the effectiveness of a new booster would be blunted by a quirk of the immune system known as imprinting — the tendency for someone’s initial exposure to a virus to bias their immune response when they meet the same virus again.

Imprinting was first observed decades ago, in people with influenza. Their immune systems responded to a new circulating strain by producing antibodies tailored to their first flu encounter. In some cases, this led to a poorer ability to fight off the new strain.

The phenomenon can explain some observations from the past, such as the surprisingly high mortality among young adults during the 1918 influenza pandemic. Members of the older generation, exposed in their youth to a flu strain that closely matched the deadly H1N1 pandemic strain, had a more robust immune response than did younger adults, whose first exposure was to a mismatched strain.

A crop of studies is now showing how imprinting is shaping people’s response to SARS-CoV-2. For example, those infected with the earliest strain or with the subsequent Alpha or Beta strains mount varying immune responses to a later Omicron infection, depending on the strain to which they were first exposed.

Furthermore, even exposure to Omicron itself doesn’t seem to help update the imprinted response of people previously infected with an older strain, which might explain why they can be reinfected.

Link to full article in Nature by Rachel Brazil



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