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Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.

Publication ,  Journal Article
Callaway, HM; Hastie, KM; Schendel, SL; Li, H; Yu, X; Shek, J; Buck, T; Hui, S; Bedinger, D; Troup, C; Dennison, SM; Li, K; Alpert, MD ...
Published in: Cell Rep
January 31, 2023

The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike. Most IgGs that do not neutralize Omicron bind either entirely monovalently or have some (22%-50%) monovalent occupancy. Cleavage of bivalent-binding IgGs to Fabs abolishes neutralization and binding affinity, with disproportionate loss of activity against Omicron pseudovirus and spike. These results suggest that VoC-resistant antibodies overcome mutagenic substitution via avidity. Hence, vaccine strategies targeting future SARS-CoV-2 variants should consider epitope display with spacing and organization identical to trimeric spike.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

January 31, 2023

Volume

42

Issue

1

Start / End Page

112014

Location

United States

Related Subject Headings

  • SARS-CoV-2
  • Neutralization Tests
  • Humans
  • Ethnicity
  • Epitopes
  • COVID-19
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • 31 Biological sciences
  • 1116 Medical Physiology
 

Citation

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Callaway, H. M., Hastie, K. M., Schendel, S. L., Li, H., Yu, X., Shek, J., … Saphire, E. O. (2023). Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium. Cell Rep, 42(1), 112014. https://doi.org/10.1016/j.celrep.2023.112014
Callaway, Heather M., Kathryn M. Hastie, Sharon L. Schendel, Haoyang Li, Xiaoying Yu, Jeremy Shek, Tierra Buck, et al. “Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.Cell Rep 42, no. 1 (January 31, 2023): 112014. https://doi.org/10.1016/j.celrep.2023.112014.
Callaway HM, Hastie KM, Schendel SL, Li H, Yu X, Shek J, et al. Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium. Cell Rep. 2023 Jan 31;42(1):112014.
Callaway, Heather M., et al. “Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.Cell Rep, vol. 42, no. 1, Jan. 2023, p. 112014. Pubmed, doi:10.1016/j.celrep.2023.112014.
Callaway HM, Hastie KM, Schendel SL, Li H, Yu X, Shek J, Buck T, Hui S, Bedinger D, Troup C, Dennison SM, Li K, Alpert MD, Bailey CC, Benzeno S, Bonnevier JL, Chen J-Q, Chen C, Cho H, Crompton PD, Dussupt V, Entzminger KC, Ezzyat Y, Fleming JK, Geukens N, Gilbert AE, Guan Y, Han X, Harvey CJ, Hatler JM, Howie B, Hu C, Huang A, Imbrechts M, Jin A, Kamachi N, Keitany G, Klinger M, Kolls JK, Krebs SJ, Li T, Luo F, Maruyama T, Meehl MA, Mendez-Rivera L, Musa A, Okumura CJ, Rubin BER, Sato AK, Shen M, Singh A, Song S, Tan J, Trimarchi JM, Upadhyay DP, Wang Y, Yu L, Yuan TZ, Yusko E, Peters B, Tomaras G, Saphire EO. Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium. Cell Rep. 2023 Jan 31;42(1):112014.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

January 31, 2023

Volume

42

Issue

1

Start / End Page

112014

Location

United States

Related Subject Headings

  • SARS-CoV-2
  • Neutralization Tests
  • Humans
  • Ethnicity
  • Epitopes
  • COVID-19
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • 31 Biological sciences
  • 1116 Medical Physiology