The term “imprinting” refers to the way in which an individual’s immune response to a virus is often skewed by their first encounter with that virus. Flu patients were the first to have their imprints documented decades ago. By the time they had their first experience with a newly circulating strain, their immune systems had already produced antibodies specifically targeting that particular strain. Sometimes this resulted in a diminished resistance to the novel strain.
Some historical facts may be explained by the phenomenon, such as the high death rate among young people during the 1918 influenza pandemic. When compared to younger individuals, whose first exposure to the flu was to a mismatched strain, the immune response of the elderly was stronger because they had been exposed to a flu strain that closely matched the lethal H1N1 pandemic strain in childhood.
New research demonstrates that imprinting influences how individuals react to SARS-CoV-2. Immune responses to a future Omicron infection, for instance, differ depending on whether a person was exposed to the initial strain or one of the following Alpha or Beta strains.
People who have been infected with an earlier strain may be reinfected since their Enzyme Linked Immunosorbent Assay (ELISA) imprinting response has not been updated by exposure to Omicron.
The term “ELISA imprinting response” refers to the immune memory or immune imprinting that occurs after a person is infected with a virus. In the case of SARS-CoV-2, individuals who were infected with an earlier virus strain developed a specific immune response tailored to that strain. However, the Omicron variant is a new and distinct strain with different characteristics and mutations. Because the immune system’s memory is primarily based on past exposures, it may not have the necessary immune responses to effectively combat the Omicron variant.
These days, it’s not hard to adapt mRNA vaccines to a new strain, but imprinting research shows that doing so may not greatly boost protection against infection. This undermines the notion that variant-tailored boosters can significantly limit viral transmission, despite the fact that they are obviously able to prevent catastrophic sickness.
Though imprinting does not make COVID-19 more severe than it would be in someone with no prior exposure, researchers think that variant-tailored boosters are still worth considering since they still give some protection. Whatever it is, having immunity to it is preferable. More so, there are indications that the immune system may adapt, opening the door to the prospect of enhanced immune responses in at least some individuals.
Innate Recollection of Immune Responses
The immune system is better able to fight off future attacks because to imprinting, which stores information about a previously encountered invader. Memory B cells play a pivotal role; they are created in the lymph nodes in response to the initial viral encounter. These cells then patrol the circulatory system for the same enemy, looking for the right time to mature into plasma cells and produce antibodies. The problem arises when the immune system faces a viral strain that is similar to the one it has already dealt with. The memory-B-cell response is activated in this situation rather than the generation of new, or ‘naive,’ B cells to manufacture specific antibodies. Antibodies that respond with antigens shared by both the old and new strains are called cross-reactive antibodies. They may provide some defense, but they aren’t designed specifically for the new strain.
Vaccine pioneers Jonas Salk and Thomas Francis, together with colleague Joseph Quilligan, made the first discovery of imprinting in 1947. It was discovered that patients who had the flu in the past and were subsequently vaccinated against the current circulating strain had antibodies against the earlier flu strain. Francis jokingly called it “initial antigenic sin,” however modern scientists often describe to it as “imprinting.”
Only lately have scientists shown how much this mechanism affects immunity. Gostic presented an epidemiological study in 2016 demonstrating that imprinting is more than simply a fascinating side effect. She analyzed information from the H5N1 pandemic of 2009 and the H7N9 pandemic of 2013. Both strains have features in common with seasonal flu viruses, although they originated on different branches of the influenza tree.
Your subsequent immune response upon exposure to live SARS-CoV-2 is imprinted on your infection history, as well as your immunization history taken together.
Prior to the appearance of Omicron, they investigated the immune system reactions of people who had received two vaccinations. There were some who were infected before they had their injections, and others who did so later. The study’s authors discovered that prior infection or immunization had a major impact on a person’s ability to fend off infection from future strains.
A follow-up study on immunity among persons who got Omicron after receiving triple vaccination, but who had previously been exposed to COVID-19 in different ways, was published last June. Once again, they saw a wide range of reactions that pointed to imprinting from prior experience. People whose initial COVID-19 infection was with Omicron still showed antibodies that were more closely matched to the vaccine strain as well as the earlier Alpha and Delta strains.
The capacity to generate Omicron-adapted antibodies was not enhanced for individuals who had been infected with the original strain and vaccinated. This, according to Boyton, is evidence of imprinting and helps explain the prevalence of Omicron reinfections; yet, for the vast majority of individuals, even an imprinted reaction is sufficient to prevent life-threatening sickness.
Research by Yunlong Cao of Beijing’s Peking University released last month lends credence to this theory. Those who had been immunized against the original strain but who got Omicron had antibodies that were mostly reactive to both strains, but seldom specific to Omicron. Those who had never had a vaccine produced antibodies that were a perfect match for Omicron. Cao claims that the number of antibodies capable of neutralizing the second strain reduced as the two strains drifted apart. He believes that the most recent Omicron varieties, such XBB, will have an even greater impact.