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Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

Publication ,  Journal Article
Kapingidza, AB; Marston, DJ; Harris, C; Wrapp, D; Winters, K; Mielke, D; Xiaozhi, L; Yin, Q; Foulger, A; Parks, R; Barr, M; Newman, A ...
Published in: Nat Commun
November 30, 2023

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

November 30, 2023

Volume

14

Issue

1

Start / End Page

7897

Location

England

Related Subject Headings

  • Spike Glycoprotein, Coronavirus
  • SARS-CoV-2
  • Peptides
  • Mice
  • Immunodominant Epitopes
  • Humans
  • Epitopes
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • Animals
 

Citation

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Kapingidza, A. B., Marston, D. J., Harris, C., Wrapp, D., Winters, K., Mielke, D., … Azoitei, M. L. (2023). Engineered immunogens to elicit antibodies against conserved coronavirus epitopes. Nat Commun, 14(1), 7897. https://doi.org/10.1038/s41467-023-43638-9
Kapingidza, A Brenda, Daniel J. Marston, Caitlin Harris, Daniel Wrapp, Kaitlyn Winters, Dieter Mielke, Lu Xiaozhi, et al. “Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.Nat Commun 14, no. 1 (November 30, 2023): 7897. https://doi.org/10.1038/s41467-023-43638-9.
Kapingidza AB, Marston DJ, Harris C, Wrapp D, Winters K, Mielke D, et al. Engineered immunogens to elicit antibodies against conserved coronavirus epitopes. Nat Commun. 2023 Nov 30;14(1):7897.
Kapingidza, A. Brenda, et al. “Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.Nat Commun, vol. 14, no. 1, Nov. 2023, p. 7897. Pubmed, doi:10.1038/s41467-023-43638-9.
Kapingidza AB, Marston DJ, 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 JM, Harner A, Catanzaro NJ, Mallory ML, Mattocks MD, Beverly C, Rhodes B, Mansouri K, Van Itallie E, Vure P, Dunn B, Keyes T, Stanfield-Oakley S, Woods CW, Petzold EA, Walter EB, Wiehe K, Edwards RJ, Montefiori DC, Ferrari G, Baric R, Cain DW, Saunders KO, Haynes BF, Azoitei ML. Engineered immunogens to elicit antibodies against conserved coronavirus epitopes. Nat Commun. 2023 Nov 30;14(1):7897.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

November 30, 2023

Volume

14

Issue

1

Start / End Page

7897

Location

England

Related Subject Headings

  • Spike Glycoprotein, Coronavirus
  • SARS-CoV-2
  • Peptides
  • Mice
  • Immunodominant Epitopes
  • Humans
  • Epitopes
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • Animals