CoChat
Sign Up
PreprintCited by 26SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesAnimal Virus Infections Studies

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Engineered Immunogens to Elicit Antibodies Against Conserved Coronavirus Epitopes

Open access
Kapingidza, Brenda, Marston, Daniel J., Harris, Caitlin, Wrapp, Daniel, Winters, Kaitlyn, Mielke, Dieter, Xiaozhi, Lu, Yin, Qi, Foulger, Andrew, Parks, Rob, Barr, Maggie, Newman, Amanda, Schäfer, Alexandra, Eaton, Amanda, Flores, Justine Mae, Harner, Austin, Cantazaro, Nicholas J, Mallory, Michael L, Mattocks, Melissa D, Beverly, Christopher, Rhodes, Brianna, Mansouri, Katayoun, Itallie, Elizabeth Van, Vure, Pranay, Manness, Brooke, Keyes, Taylor, Stanfield-Oakley, Sherry, Woods, Christopher W., Petzold, Elizabeth A., Walter, Emmanuel B, Wiehe, Kevin, Edwards, Robert J., Montefiori, David, Ferrari, Guido, Baric, Ralph, Cain, Derek W., Saunders, Kevin O., Haynes, Barton F., Azoitei, Mihai L.·2023·Nature Communications
DOI 10.1101/2023.02.27.530277PMC PMC10689493

Preprint — published as 10.1038/s41467-023-43638-9

Open this paper in CoChat — free accountOpen PDF

Abstract

Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employed computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant RBD. These engineered proteins bound with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interacted with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicited sera with broad betacoronavirus reactivity and protected as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2023.02.27.530277

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 51

  1. 10.1016/j.cell.2020.09.037 · DOI · Paper page
  2. 10.1038/s41586-021-03324-6 · DOI · Paper page
  3. 10.1126/sciimmunol.abi6950 · DOI · Paper page
  4. 10.1038/s41586-020-2456-9 · DOI · Paper page
  5. 10.1371/journal.ppat.1010951 · DOI
  6. 10.1016/j.chom.2022.11.012 · DOI
  7. 10.1126/science.abq3773 · DOI
  8. 10.1126/science.abq2679 · DOI
  9. 10.1126/science.abj3321 · DOI
  10. 10.1126/scitranslmed.abi9215 · DOI
  11. 10.1016/j.molcel.2022.03.028 · DOI
  12. 10.1016/j.celrep.2022.111009 · DOI
  13. 10.1016/j.chom.2022.10.010 · DOI
  14. Zhou, P. et al. Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause severe disease. (Immunology, 2022). · DOI
  15. 10.1126/science.1209368 · DOI · Paper page
  16. 10.1016/j.str.2010.06.010 · DOI
  17. 10.1073/pnas.1004728107 · DOI · Paper page
  18. 10.1073/pnas.1004728107 · DOI · Paper page
  19. 10.1101/685867 · DOI
  20. 10.1016/j.cell.2021.06.021 · DOI
  21. 10.1126/science.add2187 · DOI · Paper page
  22. 10.1016/j.chom.2022.10.010 · DOI
  23. 10.1016/j.jviromet.2009.02.014 · DOI
  24. 10.1021/acsnano.8b02805 · DOI
  25. 10.1038/s41586-021-03594-0 · DOI · Paper page
  26. 10.3389/fimmu.2021.637651 · DOI
  27. 10.1016/j.jmb.2011.10.003 · DOI
  28. 10.1126/science.add2187 · DOI · Paper page
  29. 10.1002/prot.24641 · DOI
  30. 10.1016/j.str.2010.06.010 · DOI
  31. 10.1016/j.jmb.2011.04.044 · DOI
  32. 10.1038/nature12966 · DOI · Paper page
  33. 10.1038/s41586-021-03819-2 · DOI · Paper page
  34. 10.1126/scitranslmed.aat0381 · DOI
  35. 10.1126/science.add6502 · DOI
  36. 10.1016/j.immuni.2023.02.005 · DOI
  37. 10.1038/s41467-022-33985-4 · DOI
  38. 10.1126/scitranslmed.abj7125 · DOI
  39. 10.1107/S0907444910048675 · DOI
  40. 10.1107/S0907444913000061 · DOI
  41. 10.1107/S0907444906045975 · DOI
  42. 10.1107/S0907444904019158 · DOI · Paper page
  43. 10.1107/S2059798318002425 · DOI
  44. 10.1107/S0907444909052925 · DOI · Paper page
  45. 10.1016/j.jviromet.2009.02.014 · DOI
  46. 10.3389/fimmu.2014.00170 · DOI
  47. 10.1126/science.abm3425 · DOI · Paper page
  48. 10.1002/cyto.a.24552 · DOI
  49. 10.1371/journal.pone.0173778 · DOI
  50. 10.7554/eLife.42166 · DOI
  51. 10.1073/pnas.1517719113 · DOI · Paper page

Metadata

Authors
Kapingidza, B., Marston, D. J., Harris, C., Wrapp, D., Winters, K., Mielke, D., Xiaozhi, L., Yin, Q., Foulger, A., Parks, R., Barr, M., Newman, A., Schäfer, A., Eaton, A., Flores, J. M., Harner, A., Cantazaro, N. J., Mallory, M. L., Mattocks, M. D., Beverly, C., Rhodes, B., Mansouri, K., Itallie, E. V., Vure, P., Manness, B., Keyes, T., Stanfield-Oakley, S., Woods, C. W., Petzold, E. A., Walter, E. B., Wiehe, K., Edwards, R. J., Montefiori, D., Ferrari, G., Baric, R., Cain, D. W., Saunders, K. O., Haynes, B. F., & Azoitei, M. L.
Affiliations
  • Duke University (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Azoitei, Mihai L.
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2023-02-28
Volume
14
Issue
1
Pages
7897-7897
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2023.02.27.530277
PMC
PMC10689493
OpenAlex
W4389183324
Cited by
26
References
1
Citations by year
2026: 7 · 2025: 12 · 2024: 5 · 2023: 2
FWCI
5.35
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Energy (Contract No. W-31-109-Eng-38, W - 31 - 109 - Eng - 38)
  • U.S. Department of Health and Human Services (R01AI155804, P01AI158571)
  • Office of Science (W-31-109-ENG-38)
  • National Institute of Allergy and Infectious Diseases (R01AI155804, P01AI158571, T32AI007392)
  • Basic Energy Sciences (W-31-109-Eng38)
  • Argonne National Laboratory (W-31-109-ENG-38)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
SARS-CoV-2, spike protein, conserved epitopes, broadly neutralizing antibodies, fusion peptide, receptor binding domain, monoclonal antibodies, vaccine design, betacoronaviruses, antibody escape

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review