Researchers identify other parts of the virus that could be targeted by COVID-19 vaccines

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Peer-reviewed: This work was reviewed and scrutinised by relevant independent experts.

Experimental study: At least one thing in the experiment was changed to see if it had an impact on the subjects (often people or animals) – eg: changing the amount of time mice spend on an exercise wheel to find out what impact it has on weight loss.

Cells: This is a study based on research in micro-organisms, cells, tissue, organs or non-human embryos.

The available COVID-19 vaccines are all designed to trigger our bodies to make antibodies against a part of the virus called the spike protein. But US researchers say we may also be able to develop immune responses against other parts of the virus after they mapped 79 “epitopes” – specific parts of the virus that antibodies recognise and bind to. They found previously unknown epitopes throughout the full array of proteins in SARS-CoV-2 and other coronaviruses, expanding the potential for future vaccine and therapeutic development.

Journal/conference: PLOS Biology

Link to research (DOI): 10.1371/journal.pbio.3001265

Organisation/s: University of Wisconsin-Madison, USA

Funder: 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.

Media release

From: PLOS

SARS-Cov-2 infections may trigger antibody responses against multiple virus proteins

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”.



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