Some people are better at fighting off seasonal flu when the strain is similar to the first one they encountered in childhood. There is increasing evidence that people's immune responses could be shaped by previous infections with common-cold coronaviruses.
The design of future COVID-19 vaccines could be affected by the effect. It's not clear what effect it has on people with COVID-19, and whether it provides enhanced protection or hampers the immune response. Craig Thompson is a researcher at the University of Oxford, UK.
In 1960, Thomas Francis Jr., a US epidemiologist, noticed that the immune system seemed to be permanently programmed to produce antibodies against the first strain of a flu virus. When the body is exposed to a flu virus that shares regions, the immune cells are able to come back to life.
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There is growing evidence that exposure to other coronaviruses plays a part in people's immune responses. Scott Hensley, a microbiologist at the University of Pennsylvania, says that most of us are exposed to coronaviruses by the age of five or six. The group discovered that blood samples taken from people before the outbreak contained an anti-OC43 antibodies that could bind to the spike protein of the coronaviruses.
Hensley and his colleagues were able to show that the production of OC43-binding antibodies was boosted by catching the disease. The structure of the S2 subunit of the SARS-CoV-2 spike protein is similar to that in OC 43, according to a study published in April. The OC43 was unable to stop the virus from entering cells because it did not bind to the S1 region.
There are effects of imprinting.
In some cases, imprinting can have a positive effect on immunity. Exposure to some historical flu strains provided protection against H1N1 infections, according to a study by Hensley and his colleagues. There were some similarities between that virus and past seasonal flu strains. The recall of responses against those epitopes was beneficial.
There are potential downsides to OAS. Sometimes, the production of antibodies as a result of imprinting is not a good match to the virus causing an infection, but it does not affect the production of naive B cells that would otherwise produce more protective antibodies. The director of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai in New York City says that a response may be skewed towards conserved antigens. The immune system can be affected by this.
There was an increase in the levels of antibodies against both OC 43 and HKU1 in people hospitalized with COVID-19 in Spain. There was a correlation between people with higher levels of antibodies against the conserved epitopes and people with less protective immunity against the coronaviruses.
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The signs of OAS negatively affecting people with COVID-19 were seen by Thompson and his colleagues. The analysis was based on samples taken from people in the United Kingdom who had infections and from people who were admitted to the hospital with severe COVID-19. The researchers found that people who died produced less anti-SRS-CoV-2 antibodies than people who survived, but they produced the same amount of anti-SRS-CoV-2 antibodies.
The results show that imprinted memories of the spike protein from a different coronaviruses could be preventing a more effective immune response in those who did not survive. He says it's a fingerprints of OAS. He says it is too early to conclude this.
The results of preliminary studies are open to interpretation and it is difficult to tell if OAS is beneficial or detrimental to the immune response. A full picture of a complex immune response is not provided by just measuring antibody levels. He thinks the presence of OC43 antibodies in people with COVID-19 could be a sign that the immune system is fighting the virus. A study of samples from health-care workers showed that people with higher OC43 levels recovered from the disease quicker than those with lower levels. Similar protective effects have been shown in other research.
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In a study published in December 2020, George Kassiotis, an immunologist at the Francis Crick Institute in London, found that pre-existing OC43 antibodies showed reactivity to the disease. He wasn't sure of the implications at the time, but after reviewing studies published since, he says, "most of the evidence points to a positive overall contribution, not a negative one."
Even if they are not able to stop the disease from entering cells, the immune system might be able to kill it.
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The vaccine is updated.
The question is whether these observations can help to inform future COVID-19 vaccination strategies. The original version of the coronaviruses protects against all known versions.
Sarah Cobey, an evolutionary biologist and flu researcher at the University of Chicago, says that Imprinting can reduce the effectiveness of flu vaccines. Each year the flu vaccine is updated to protect against strains that are most likely to be present. Some people's immune systems are still not seeing the update, and still target parts of the virus that are familiar to them. It looks like they aren't really responding to the thing that we updated the vaccine for. It is possible that future COVID-19 vaccines could have similar problems.
Hensley doesn't think this is likely. He and his colleagues reported in a study published last month that people don't produce as many OC43 antibodies after receiving a messenger RNA vaccine. The immune-imprinting effect can be bypassed by the efficient immune response of the vaccine. In the case of the vaccine, there might not be as much bias towards the conserved epitopes. That is the hope, says Hensley.
Thompson says that the problem could be solved by removing the S2 domain from the updated COVID-19 vaccine. This is not realistic.
There is a very complicated interplay between seasonal coronaviruses and disease outcomes. I don't think anything should be presented as complete fact at this point.
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The article was first published in November of 2021.
