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SARS-CoV-2 Triggers Antibodies From Previous Coronavirus Infections

A large fraction of non-exposed individuals have T cell reactivity to COVID-19 peptides.

Investigators from Northern Arizona University and the Translational Genomics Institute have suggested that people’s immune systems who are infected with the coronavirus disease 2019 (COVID-19) may rely on antibodies that were created during previous infections with earlier coronaviruses, aiding the fight against the current disease. The data from the study was published in the journal Cell Reports Medicine.

The study employed a novel technology called PepSeq, a tool that allows for the construction of diverse pools of peptides that are bound to DNA tags. Investigators then finely mapped antibody responses to all known infecting coronaviruses. Combining this data with high-throughput sequencing allows for a deep interrogation of antibody responses to the viruses.

"The data generated using PepSeq allowed for broad characterization of the antibody response in individuals recently infected with SARS-CoV-2 compared with those of individuals exposed only to previous coronaviruses that now are widespread in human populations," Jason Ladner, an Assistant Professor at NAU's Pathogen and Microbiome Institute and lead author on the study said.

After characterizing the antibodies that recognize the SARS-C0V-2 virus, the investigators examined responses to four older coronaviruses, including alphacoronavirus 229E; alphacoronavirus NL63; betacoronavirus OC43; and betacoronavirus HKU1. These viruses are much more common throughout the human population and are not usually deadly, causing only mild illness.

When comparing reactivity patterns against the different viruses, investigators demonstrated that the COVID-19 virus could use immune system antibodies that were originally generated in response to previous infections with other coronaviruses. The observed cross-reactivity took place in 2 sites on the virus’s spike protein, which it uses to attach to the ACE2 protein and infiltrate cells.

"Our findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous coronavirus exposures, and which have potential to raise broadly-neutralizing antibodies,” John Altin, senior author on the study said. “We further demonstrate that these cross-reactive antibodies preferentially bind to endemic coronavirus peptides, suggesting that the response to SARS-CoV-2 at these regions may be constrained by previous coronavirus exposure.