LONDON: The first SARS-CoV-2 spike protein that a person encounters, be it through vaccination or infection, shapes their body's subsequent immune response against current and future variants, according to a study conducted in the UK.
The study finds that exposure to the virus imparts different properties that have an impact on the immune system's ability to protect against current and future variants, and also affects the rate of decay of protection, which explains why populations across different regions and countries build varying degrees of immunity to similar virus strains.
Orchestrated by a team of scientists from the Imperial College and Queen Mary University of London, their findings were published in the journal 'Science' on Friday.
"Our first encounter with spike antigen either through infection or vaccination shapes our subsequent pattern of immunity through immune imprinting," said Professor Rosemary Boyton, from Imperial College's Department of Infectious Disease.
"Exposure to different spike proteins can result in reduced or enhanced responses to variants further down the line. This has important implications for future proofing vaccine design and dosing strategies," she said.
It is known that antibody levels wane over time following infection or vaccination, but the new research shows that an individual's protective immune responses are also affected by which strain or combination of strains they have been exposed to.
Each SARS-CoV-2 variant has different mutations in the spike protein, and the researchers found that they shape the subsequent antibody and T-cell responses, or the body's immune repertoire.
"This study now offers considerable new details about who is susceptible and when. You can be someone who made a great response to the vaccine and still fall prey to Delta breakthrough if you haven't had a booster," said Professor Danny Altmann from Imperial College's Department of Immunology and Inflammation.
"Immune imprinting means we're now all walking around programmed slightly differently for our future protection. The challenge is how to broaden the population's immunity in the right way as we need to ensure the widest coverage possible."
"Currently, with the Omicron variant emerging, it's vital that people get their booster vaccines. But in the future, we should consider how we can create vaccines that broaden our immune response even more to protect against other new variants of concern," he explained.
Based on their findings, the researchers say that vaccine design and dosing strategies need to be proofed to take maximum advantage of immune imprinting.
This will involve enhancing the breadth of protection rather than tweaking the vaccines with the latest variant spike sequences.
"The emergence of new variants with the potential to evade immunity has shown that we must future-proof the next-generation of vaccines."
"We studied immunity over time in people infected with different variants and found that vaccine responses are highly variable depending on the infecting strain. These findings can be used to ensure vaccine design is optimal. This work highlights the importance of continually monitoring the effectiveness of vaccines against new variants such as Omicron," Dr Joseph Gibbons, from Queen Mary University of London explained.
The research, funded by UK Research and Innovation (UKRI), looked at "immune imprinting" in healthcare workers after two doses of the Pfizer/BioNTech vaccine to understand their immune response to infection by variants of concern.
It involved detailed, longitudinal follow-up of the Barts Health National Health Service (NHS) Trust COVIDsortium healthcare worker cohort of 731 individuals, who have been followed since March 2020.
The study revealed that neutralising antibody responses against variants decay differentially over time after mixed spike encounters.
There were a number of cases of Delta breakthrough infection in two dose vaccinated individuals in the study.
Levels of spike antibodies measured three weeks after the second vaccine dose were high, yet the actual levels of protective neutralising antibody responses against Delta had fallen to zero, five months after their second dose.
However, a third dose of the original spike from a booster vaccine uplifted the antibody responses.
"These findings highlight the importance of third dose booster vaccination to reduce viral transmission," Professor Boyton said.
Overall, the researchers stress that, despite breakthrough infections being seen, immune responses to vaccination are still effective in preventing severe disease and death from COVID-19 in the face of Alpha, Beta, Gamma and Delta variants.
The new Omicron variant remains under study, but the researchers believe the so-called "immune imprinting" could mean a very different impact of the mutation in different parts of the world.