SARS-CoV-2 triggers antibodies from previous coronavirus infections

The results of a new study have suggested that the immune systems of people infected with COVID-19 may rely on antibodies created during infections from earlier coronaviruses to help fight the disease.

The study was conducted at Northern Arizona University and the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, both US. 

According to the researchers, humans have come into contact with at least six other types of coronaviruses previously. In their study, the team sought to understand how coronaviruses (CoVs) ignite the human immune system and investigate the inner workings of the antibody response. 

“Our results suggest that the COVID-19 virus may awaken an antibody response that existed in humans prior to our current pandemic, meaning that we might already have some degree of pre-existing immunity to this virus.” said Assistant Professor John Altin, the study’s senior author.

This knowledge could help researchers design new diagnostics, evaluate the healing powers of convalescent plasma, develop new therapeutic treatments and help design future vaccines or monoclonal antibody (mAb) therapies capable of protecting against mutations that may occur in the COVID-19 virus.

The researchers used a tool called PepSeq to map antibody responses to all human-infecting coronaviruses. PepSeq is a novel technology that allows for the construction of highly diverse pools of peptides bound to DNA tags. When combined with high-throughput sequencing, these PepSeq molecule pools allow for deep interrogation of the antibody response to viruses.

“The data generated using PepSeq allowed for broad characterisation 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,” said Assistant Professor Jason Ladner, the study’s lead author. 

Besides SARS-CoV-2, researchers examined the antibody responses from two other potentially deadly coronaviruses: MERS-CoV and SARS-CoV-1. In addition to characterising antibodies that recognise SARS-CoV-2, they also examined the antibody responses of four older coronaviruses: alphacoronavirus 229E; alphacoronavirus NL63; betacoronavirus OC43; and betacoronavirus HKU1. 

By comparing patterns of reactivity against these different coronaviruses, the researchers demonstrated that SARS-CoV-2 could summon immune system antibodies originally generated in response to past coronavirus infections. This cross-reactivity occurred at two sites in the SARS-CoV-2 Spike (S) protein.

“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-neutralising antibodies. 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,” said Altin.

According to the researchers, these findings could help explain the widely varying reactions COVID-19 patients have to the disease, from mild to no symptoms, to severe infections requiring hospitalisation and often resulting in death. 

“Our findings raise the possibility that the nature of an individual’s antibody response to prior endemic coronavirus infection may impact the course of COVID-19 disease,” Ladner said.

The findings were published in Cell Reports Medicine.