[ad_1]
Results from a study led by Northern Arizona University and the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that the immune systems of people infected with COVID-19 may be dependent on antibodies. created during previous coronavirus infections to help fight the disease.
COVID-19 is not humanity’s first encounter with a coronavirus, named for the corona, or corona-shaped protein spikes on its surface. Before SARS-CoV-2, the virus that causes COVID-19, humans had navigated at least 6 other types of coronavirus.
The study sought to understand how coronaviruses (CoVs) turn on the human immune system and take a deeper dive into the inner workings of the antibody response. The published findings, “Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses,” appear in the journal. Cell Report Medicine.
“Our results suggest that the COVID-19 virus may elicit an antibody response that existed in humans before our current pandemic, which means that we may already have some degree of pre-existing immunity to this virus.” said John Altin, assistant professor in TGen’s branch of infectious diseases and lead author of the study.
This knowledge could help researchers design new diagnoses, evaluate the healing powers of convalescent plasma, develop new therapeutic treatments and, most importantly, help design future vaccines or monoclonal antibody therapies capable of protecting against mutations that can occur in the COVID-19 virus.
The researchers used a tool called PepSeq to accurately map antibody responses to all coronaviruses that infect humans. PepSeq is a new technology being developed at TGen and NAU that allows the construction of very diverse groups of peptides (short chains of amino acids) linked to DNA tags. When combined with high-throughput sequencing, these sets of PepSeq molecules allow in-depth interrogation of the antibody response to viruses.
“The data generated with PepSeq allowed for a broad characterization of the antibody response in individuals recently infected with SARS-CoV-2 compared to individuals exposed only to earlier coronaviruses that are now widespread in human populations,” said Jason Ladner, study leader. author and assistant professor at the NAU Institute of Pathogens and Microbiome.
In addition to SARS-CoV-2, the researchers examined the antibody responses of two other life-threatening coronaviruses: MERS-CoV, which triggered the 2012 Middle East respiratory syndrome outbreak in Saudi Arabia; and SARS-CoV-1, the first pandemic coronavirus that caused the outbreak of severe acute respiratory syndrome in Asia in 2003. All three are examples of coronaviruses that infect animals, but evolved to make people sick and became new pathogens humans.
In addition to characterizing the antibodies that recognize SARS-CoV-2, they also examined the antibody responses of four older coronaviruses: alphacoronavirus 229E; alphacoronavirus NL63; OC43 betacoronavirus; and betacoronavirus HKU1. These so-called “common” coronaviruses are endemic in human populations, but are generally not fatal and cause mild upper respiratory infections similar to those of the common cold.
By comparing the 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 on the SARS-CoV-2 spike protein; the protein on the surface of virus particles that attaches to ACE2 proteins in human cells to facilitate cell entry and infection.
“Our findings highlight the sites where the response to SARS-CoV-2 appears to be determined by previous exposures to the coronavirus and which have the potential to generate broadly neutralizing antibodies. Furthermore, we demonstrated that these cross-reactive antibodies preferentially bind to endemic coronavirus peptides, suggesting that the response to SARS-CoV-2 in these regions may be limited by previous exposure to the coronavirus, ”Altin said, adding that More research is needed to understand the implications of these findings.
Outbreak News Interview Podcast on Spotify
The findings could help explain the widely variable reactions that COVID-19 patients have to the disease; from mild to no symptoms to severe infections that require hospitalization and often lead to death. It is also possible that the differences in pre-existing antibody response identified by this study may help explain some of the differences in the severity of COVID-19 disease manifestation in older versus younger people, who will have different histories of infections with common coronaviruses.
“Our findings raise the possibility that the nature of an individual’s antibody response to a previous endemic coronavirus infection may affect the course of COVID-19 disease,” Ladner said.
Also contributing to this study were: City of Hope National Medical Center, Walter Reed National Military Medical Center, Vitalant Research Institute, Sanford Burnham Prebys Medical Discovery Institute, Norwegian University of Science and Technology, St. Olavs Hospital, and Encodia Inc.
Former computer science college student Zane Fink is named a co-author of the study. “Zane was very helpful with the design of the trials used and wrote custom analysis software,” Ladner said. Fink, who graduated from NAU in the spring of 2020, is now pursuing a doctorate in computer science at the University of Illinois.
