
6/27/2022
In the study, online now in Cell Reports, the team performed the most comprehensive analysis to date of COVID-19 antibodies in a small set of patients with severe disease. They found that antibody profiles of internal viral proteins, including those conserved across coronaviruses, predicted which patients survived or died just as well as corresponding profiles for surface proteins, suggesting that targeting other parts of the virus beyond the spike protein could be important for enhancing COVID-19 vaccines and therapies.

When the immune system encounters a virus, it produces antibodies that help neutralize and clear the infection. Each antibody specifically recognizes just one antigen, often a viral protein. Most COVID-19 immunity research has focused on the spike and other surface proteins, which form the virus’s outer coat, but beyond these so-called “canonical antigens,” SARS-CoV-2 has about 25 other internal proteins.
The researchers analyzed blood samples that had been collected from 21 patients who were hospitalized with severe COVID-19 in 2020 — prior to the approval of vaccines. Seven of these patients died from the disease, and the other 14 survived. Using a microscale antibody profiling platform developed by Sarkar, the team comprehensively analyzed antibodies to three canonical and four non-canonical antigens.
“By simultaneously profiling these three features, we can get a far deeper understanding of a given antibody than just looking at antibody titers,” explained Sarkar.

Most COVID-19 vaccines and monoclonal antibodies — artificial antibodies used to treat COVID-19 —have become less effective with the emergence 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 augmenting vaccines or therapies to target these non-canonical antigens could elicit more robust immunity against emerging variants of concern.
According to Das, these findings could inform development of pan-coronavirus vaccines.
Other authors who contributed to this study were co-first authors Sai Preetham Peddireddy, of the Georgia Institute of Technology, and Syed A. Rahman, Ph.D., of Pitt, as well as Anthony R. Cillo, Ph.D., Godhev Manakkat Vijay, Ph.D., Ashwin Somasundaram, M.D., Creg J. Workman, Ph.D., William Bain, M.D., Bryan J. McVerry, M.D., Barbara Methe, Ph.D., Janet S. Lee, M.D., Prabir Ray, Ph.D., Anuradha Ray, Ph.D., Tullia C. Bruno, Ph.D., Dario A.A. Vignali, Ph.D., Georgios D. Kitsios, M.D., Ph.D., and Alison Morris, M.D., all of Pitt.
Top Left Photo:
PHOTO DETAILS: (click images for high-res versions)
CREDIT: University of Pittsburgh
CAPTION: Jishnu Das, Ph.D., assistant professor of immunology and of computational and systems biology in the University of Pittsburgh School of Medicine
Middle Right Photo:
PHOTO DETAILS: (click images for high-res versions)
CREDIT: Georgia Institute of Technology and Emory University
CAPTION: Aniruddh Sarkar, Ph.D., assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University
Bottom Left Photo:
PHOTO DETAILS: (click images for high-res versions)
CREDIT: University of Pittsburgh
CAPTION: Harinder Singh, Ph.D., professor of immunology and the director of the Center for Systems Immunology at the University of Pittsburgh