SARS-CoV-2 Infections May Trigger Antibody Responses Against Multiple Virus Proteins (Biology)

Study suggests vaccines, therapeutics, and diagnostics should not be limited to spike protein

All coronaviruses produce four primary structural proteins and multiple nonstructural proteins. However, the majority of antibody-based SARS-CoV-2 research has focused on the spike and nucleocapsid proteins. A study published in PLOS Biology by Anna Heffron, Irene Ong and colleagues at the University of Wisconsin-Madison, USA, suggests that immune responses may develop against other proteins produced by the SARS-CoV-2 virus.

The efficacy of spike protein-based vaccines is variable and not everyone infected with SARS-CoV-2 produces detectable antibodies against the spike or nucleocapsid proteins. Therefore, expanded antibody-based options have the potential to play an important role in improving vaccines, diagnostics, and therapeutics, particularly given the emergence of new variants. To investigate whether SARS-CoV-2 infection induces robust antibody responses against all SARS-CoV-2 proteins, researchers mapped 79 “epitopes” – specific regions of the viral proteome that antibodies recognize and bind to. They also tested whether antibodies that develop in response to SARS-CoV-2 or existing antibodies from previous exposures to coronaviruses might bind to any of the proteins in the six other known human coronaviruses to identify potential cross-reactive epitopes.

In addition to spike and nucleocapsid proteins, the authors located previously unknown, highly reactive B cell epitopes throughout the full array of proteins in SARS-CoV-2 and other coronaviruses, expanding the potential for future vaccine and therapeutic development. Future research is needed, however, to determine how long these antibodies remain and whether responses of vaccinated individuals differ from those who contracted COVID-19 prior to vaccination. Dr. Ong and colleagues will continue to investigate these aspects in adults and children.

Although the authors did not directly profile variants of concern that have emerged since the beginning of the COVID-19 pandemic, a comparison of the original SARS-CoV-2 genome with a few of the variants of concern identified numerous variations in regions that are at or within 3 amino acids of identified antibody binding epitopes.

According to the authors, “Our extensive profiling of epitope-level resolution antibody reactivity in COVID-19 convalescent subjects, confirmed by independent assays, provides new epitopes that could serve as important targets in the development of improved diagnostics, vaccines, and therapeutics against SARS-CoV-2, variants of concern, and dangerous human coronaviruses that may emerge in the future”.


Research Article

Peer reviewed; Experimental study; Cells

In your coverage please use these URLs to provide access to the freely available articles in PLOS Biology

Funding: I.M.O. acknowledges support by the Clinical and Translational Science Award (CTSA) program (, through the National Institutes of Health National Center for Advancing Translational Sciences (NCATS), grants UL1TR002373 and KL2TR002374. This research was also supported by 2U19AI104317-06 (to I.M.O via James Gern) and R24OD017850 (to D.H.O.) from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health ( A.S.H. has been supported by the National Institutes of Health National Research Service Award T32 AI007414 and M.F.A. by T32 AG000213 ( S.J.M. acknowledges support by the National Cancer Institute, National Institutes of Health and University of Wisconsin Carbone Comprehensive Cancer Center’s Cancer Informatics Shared Resource (grant P30-CA-14520; and by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health 2U19AI104317-06. This project was also funded through a COVID-19 Response Grant from the Wisconsin Partnership Program and the University of Wisconsin School of Medicine and Public Health (to M.A.S.;, startup funds through the University of Wisconsin Department of Obstetrics and Gynecology (I.M.O.;, and the Data Science Initiative ( grant from the University of Wisconsin-Madison Office of the Chancellor and the Vice Chancellor for Research and Graduate Education (with funding from the Wisconsin Alumni Research Foundation) (I.M.O.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: The authors declare the following competing interests: A.S.H., S.J.M., D.A.B., M.F.A., S.K., M.A.S., D.H.O., and I.M.O are listed as the inventors on a patent filed that is related to findings in this study. Application: 63/080568, 63/083671. Title: IDENTIFICATION OF SARS-COV-2 EPITOPES DISCRIMINATING COVID-19 INFECTION FROM CONTROL AND METHODS OF USE. Application type: Provisional. Status: Filed. Country: United States. Filing date: September 18, 2020, September 25, 2020.

Reference: Heffron AS, McIlwain SJ, Amjadi MF, Baker DA, Khullar S, Armbrust T, et al. (2021) The landscape of antibody binding in SARS-CoV-2 infection. PLoS Biol 19(6): e3001265.

Provided by PLOS

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