Antibody profiles of intrinsic viral proteins predict severe COVID-19 results

Antibody profiles of intrinsic viral proteins predict severe COVID-19 results

Most research on SARS-CoV-2 immunity and COVID-19 vaccine development has focused on antibody responses to spike protein and other viral surface proteins. But antibodies that recognize the virus’s intrinsic proteins may also be important for immunity and disease outcomes, according to a new study by researchers at the University of Pittsburgh, the Georgia Institute of Technology and Emory University.

In the study, now online at Cell messages, the team performed the most comprehensive analysis of COVID-19 antibodies to date in a small group of patients with severe disease. They found that antibody profiles of intrinsic viral proteins, including those conserved across coronaviruses, predicted which patients survived or died as well as the corresponding surface protein profiles, suggesting that targeting other parts of the virus outside the spike protein could be important to enhance COVID. -19 vaccines and therapies.

A new aspect of this study is that we performed a very deep profiling of SARS-CoV-2 antibodies and looked at many different aspects of these antibodies. The whole world has focused on the spike protein and receptor binding domain, but this study is the first concrete evidence that specific antibodies to intrinsic proteins are also positively associated with survival in heavy COVID-19. “

Jishnu Das, Ph.D., co-author, Assistant Professor of Immunology and Computational and Systems Biology at Pitt’s School of Medicine

When the immune system encounters a virus, it produces antibodies that help neutralize and eliminate the infection. Each antibody specifically recognizes only one antigen, often a viral protein. Most research on COVID-19 immunity has focused on the spike and other surface proteins that make up the outer shell of the virus, but in addition to these so-called “canonical antigens,” SARS-CoV-2 has about 25 other internal proteins.

To determine whether immune responses to these non-canonical antigens can predict survival outcomes in patients with severe COVID-19, Das contacted co-authors Aniruddh Sarkar, Ph.D., an assistant professor of biomedicine at Wallace H. Coulter. Engineering at Georgia Tech and Emory University and Harinder Singh, Ph.D., Professor of Immunology and Director of the Center for Systems Immunology in Pitt.

The researchers analyzed blood samples taken from 21 patients who were hospitalized with severe COVID-19 in 2020 -; before vaccine approval. Seven of these patients died of the disease and another 14 survived. Using a micro-scale antibody profiling platform developed by Sarkar, the team comprehensively analyzed antibodies to three canonical and four non-canonical antigens.

According to Sarkar, the platform analyzes three key properties of antibodies. One is antigen specificity, or what the antibody binds to. The second is effector function, which is related to the role of the antibody in the immune response. A third feature is glycosylation, or the addition of carbohydrate molecules to the antibody, which dramatically affects antibody function.

“By simultaneously profiling these three properties, we can gain a much deeper understanding of a given antibody than just looking at antibody titers,” Sarkar explained.

The researchers found that no single property of the antibody could distinguish between patient survival outcomes. But when they analyzed the overall antibody profiles -; either canonical or non-canonical -; they noted clear differences between survivors and non-survivors.

“We were surprised to find such compelling evidence that antibodies directed to canonical and non-canonical antigens were equally predictive of survival outcomes,” Singh said. “Our findings suggest that non-canonical antibodies may play a role in recovery from severe disease, although more research is needed to establish causation and determine mechanisms.”

Most COVID-19 vaccines and monoclonal antibodies -; artificial antibodies used to treat COVID-19 – have become less effective with the formation of delta and omicron variants because mutations in the spike help the virus avoid detection. According to Singh, far fewer mutations have accumulated in the virus’s internal proteins, suggesting that the spread of vaccines or therapies targeting these non-canonical antigens could elicit stronger immunity against emerging variants of concern.

When the team limited its analysis to antibodies to non-canonical antigens preserved across coronaviruses -; including those that cause common colds and other respiratory infections -; in patients with COVID-19 they were still able to distinguish between survivors and non-survivors. These antibodies were also found in nine prepandemic healthy controls, suggesting that exposure to coronaviruses other than SARS-CoV-2 could elicit antibody responses associated with favorable results in severe COVID-19.

According to Das, these findings could inform the development of pancreaticavir vaccines.

In the ongoing work, the team uses its platform to examine antibodies in vaccinated people with breakthrough infections compared to unvaccinated individuals. They are also interested in whether different antibodies play different roles in protection against COVID-19 over time.

They also plan to expand the platform to understand antibodies in other contexts, including organ transplant rejection and other infectious diseases.


Journal link:

Peddireddy, SP, et al. (2022) Antibodies targeting conserved non-canonical antigens and endemic coronaviruses have been associated with favorable results in severe COVID-19 disease. Cell messages.

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