Engineered immunogens to elicit antibodies against conserved coronavirus epitopes

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Kapingidza A.B.
    • Other Affiliation: Duke University
  • Marston D.J.
    • Other Affiliation: Duke University
  • Harris C.
    • Other Affiliation: Duke University
  • Wrapp D.
    • Other Affiliation: Duke University
  • Winters K.
    • Other Affiliation: Duke University
  • Mielke D.
    • Other Affiliation: Duke University
  • Xiaozhi L.
    • Other Affiliation: Duke University
  • Yin Q.
    • Other Affiliation: Duke University
  • Foulger A.
    • Other Affiliation: Duke University
  • Parks R.
    • Other Affiliation: Duke University
  • Barr M.
    • Other Affiliation: Duke University
  • Newman A.
    • Other Affiliation: Duke University
  • Schäfer A.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Eaton A.
    • Other Affiliation: Duke University
  • Flores J.M.
    • Other Affiliation: Duke University
  • Harner A.
    • Other Affiliation: Duke University
  • Catanzaro N.J., Jr.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Mallory M.L.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Mattocks M.D.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Beverly C.
    • Other Affiliation: Duke University
  • Rhodes B.
    • Other Affiliation: Duke University
  • Mansouri K.
    • Other Affiliation: Duke University
  • Van Itallie E.
    • Other Affiliation: Duke University
  • Vure P.
    • Other Affiliation: Duke University
  • Dunn B.
    • Other Affiliation: Duke University
  • Keyes T.
    • Other Affiliation: Duke University
  • Stanfield-Oakley S.
    • Other Affiliation: Duke University
  • Woods C.W.
    • Other Affiliation: Duke University
  • Petzold E.A.
    • Other Affiliation: Duke University Medical Center
  • Walter E.B.
    • Other Affiliation: Duke University
  • Wiehe K.
    • Other Affiliation: Duke University
  • Edwards R.J.
    • Other Affiliation: Duke University
  • Montefiori D.C.
    • Other Affiliation: Duke University
  • Ferrari G.
    • Other Affiliation: Duke University
  • Baric R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Cain D.W.
    • Other Affiliation: Duke University
  • Saunders K.O.
    • Other Affiliation: Duke University
  • Haynes B.F.
    • Other Affiliation: Duke University
  • Azoitei M.L.
    • Other Affiliation: Duke University
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 employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact 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 elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.
Date of publication
Keyword
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
License
  • Attribution 4.0 International
Journal title
  • Nature Communications
Journal volume
  • 14
Journal issue
  • 1
Language
  • English
Version
  • Publisher
Funder
  • Office of Science, SC
  • School of Medicine, Indiana University, IUSM
  • U.S. Department of Energy, USDOE
  • National Institutes of Health, NIH
  • Duke Human Vaccine Institute
  • Basic Energy Sciences, BES, (P01AI158571, R01AI155804, W-31-109-Eng-38)
  • Advanced Photon Source
  • National Institute of Allergy and Infectious Diseases, NIAID
  • Argonne National Laboratory, ANL
ISSN
  • 2041-1723
Publisher
  • Nature Research

Relations

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details 41467_2023_Article_43638.pdf 2024-01-03 Public Download