Scientists reveal how COVID-19 affects the immune system’s ability to recognize other coronaviruses

Having a common cold does not make you immune to COVID-19, but a COVID-19 infection can increase, at least temporarily, the number of antibodies you have against coronaviruses that cause a common cold and SARS-CoV- 1 and MERS-CoV virus, all closely related. Scientists at Scripps Research have characterized coronavirus antibodies isolated from 11 people to reveal how COVID-19 affects the immune system’s ability to recognize other coronaviruses.

“Getting a better understanding of how immunity changes against this broad family of coronaviruses with COVID-19 infection is an important step toward developing better coronavirus vaccines, both for COVID-19 and for pathogen-related pathogens. future, “says Andrew Ward, PhD, professor. of Structural and Computational Integrative Biology at Scripps Research and lead author of the new article, published online this week in Advances in Science.

The SARS-CoV-2 virus that causes COVID-19 is just one of a large and diverse family of coronaviruses. Some of his relatives are equally contagious and virulent -; causing Middle East Respiratory Syndrome (MERS) and SARS Outbreak 2002-2004 -; while others, considered common cold viruses, cause much milder symptoms. In general, many of these coronaviruses have only a quarter or half of their genetic material in common with SARS-CoV-2, but individual sections of the structures of viruses, especially the tip protein that protrudes from each coronavirus; considered relatively similar among family members.

Since the onset of the COVID-19 pandemic, scientists have wondered whether people’s prior exposure to these common cold viruses affects their immunity to SARS-CoV-2 and, similarly, if COVID-19 infection could change as the immune system recognizes more. common coronavirus. Immune system antibodies to a coronavirus ear protein could also recognize other similar ear proteins as disease-causing.

In the new study, Ward’s group studied serum samples from eleven people. Eight of the samples were dated before the COVID-19 pandemic to ensure that donors had never been exposed to the SARS-CoV-2 virus, while three samples were from donors who had recently had COVID-19. In each case, the researchers measured how strongly the samples reacted with ear proteins isolated from different coronaviruses; OC43 and HKU1, both associated with common colds, along with SARS-CoV-1, MERS-CoV, and SARS-CoV-2.

Not surprisingly, only the serum of patients recovered with COVID-19 reacted with SARS-CoV-2 ear proteins. However, these samples from patients with COVID-19 also reacted more strongly than the pre-pandemic samples to the other peak proteins.

Most people have this reference immunity to common coronaviruses, and exposure to SARS-CoV-2 increases the levels of these antibodies. “

Sandhya Bangaru, first author of the new article, postdoctoral researcher at Scripps Research

Ward, Bangaru, and colleagues conducted high-resolution structural studies on serum antibodies from three of the healthy donors and the two patients with COVID-19 to determine where each antibody bound to the tip proteins. They found that most pre-pandemic coronavirus antibodies recognized a section of the OC43 and HKU1 ear proteins known as the S1 subunit, which tends to vary widely among coronaviruses. In samples from patients with COVID-19, however, the researchers identified a broader sample of antibodies, including those that recognized the S2 subunit, which varies less between different coronaviruses. In fact, some antibodies from COVID-19 patients not only bind to common cold coronaviruses, but also to the SARS-CoV- and MERS-CoV ear proteins.

“The ultimate goal of this would be to rationally design vaccines that can recognize many different coronaviruses,” says Bangaru. “Our results reveal certain patches preserved in the S2 subunit directed by naturally induced antibodies during infection, in which we want to focus.”

Because these studies were performed directly on serum antibodies, researchers do not know whether the presence of these antibodies, in any case, is sufficient to provide total immunity to coronaviruses in the most complex environment of the human immune system. The increase in the ability of convalescent sera to react to common coronaviruses appears to be the result of both increased production of new antibodies that can recognize various coronaviruses and an increase in pre-existing antibody levels specific to each virus. However, it is not clear to what extent each of these phenomena contributes to the global increase and how they would influence the natural course of VOCID. In the future, they would like to compare the antibodies of the same individuals before and after COVID-19 infection.

“Our work provides a baseline characterization of people’s antibody responses to endemic coronavirus prior to exposure to SARS-CoV-2, but there are many open-ended questions,” says Bangaru. “We hope this will lead to much more research.”

Source:

Scripps Research Institute

Magazine reference:

Bangaru, S., et al. (2022) Structural mapping of antibody landscapes to human betacoronavirus ear proteins. Advances in Science. doi.org/10.1126/sciadv.abn2911.

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