Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies

Zhongyu Zhu, Samitabh Chakraborti, Yuxian He, Anjeanette Roberts, Tim Sheahan, Dong Xiao, Lisa E. Hensley, Ponraj Prabakaran, Barry Rockx, Igor A. Sidorov, Oavide Corti, Leatrice Vogel, Yang Feng, Jae Ouk Kim, Lin Fa Wang, Ralph Baric, Antonio Lanzavecchia, Kristopher M. Curtis, Gary J. Nabel, Kanta SubbaraoShibo Jiang, Dimiter S. Dimitrov

Research output: Contribution to journalArticle

Abstract

The severe acute respiratory syndrome coronavirus (SARS-CoV) caused a worldwide epidemic in late 2002/early 2003 and a second outbreak in the winter of 2003/2004 by an independent animal-to-human transmission. The GD03 strain, which was isolated from an index patient of the second outbreak, was reported to resist neutralization by the human monoclonal antibodies (hmAbs) 80R and S3.1, which can potently neutralize isolates from the first outbreak. Here we report that two hmAbs, m396 and S230.15, potently neutralized GD03 and representative isolates from the first SARS outbreak (Urbani, Tor2) and from palm civets (SZ3, SZ16). These antibodies also protected mice challenged with the Urbani or recombinant viruses bearing the GD03 and SZ16 spike (S) glycoproteins. Both antibodies competed with the SARS-CoV receptor, ACE2, for binding to the receptor-binding domain (RBD), suggesting a mechanism of neutralization that involves interference with the SARS-CoV-ACE2 interaction. Two putative hot-spot residues in the RBD (Ile-489 and Tyr-491) were identified within the SARS-CoV spike that likely contribute to most of the m396-binding energy. Residues Ile-489 and Tyr-491 are highly conserved within the SARS-CoV spike, indicating a possible mechanism of the m396 cross-reactivity. Sequence analysis and mutagenesis data show that m396 might neutralize all zoonotic and epidemic SARS-CoV isolates with known sequences, except strains derived from bats. These antibodies exhibit cross-reactivity against isolates from the two SARS outbreaks and palm civets and could have potential applications for diagnosis, prophylaxis, and treatment of SARS-CoV infections.

Original languageEnglish (US)
Pages (from-to)12123-12128
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number29
DOIs
StatePublished - Jul 17 2007
Externally publishedYes

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SARS Virus
Severe Acute Respiratory Syndrome
Coronavirus
Monoclonal Antibodies
Disease Outbreaks
Viverridae
Antibodies
Coronavirus Infections
Zoonoses
Mutagenesis
Sequence Analysis
Glycoproteins
Viruses

Keywords

  • Epitope
  • Paratope
  • Therapeutic
  • Vaccine

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies. / Zhu, Zhongyu; Chakraborti, Samitabh; He, Yuxian; Roberts, Anjeanette; Sheahan, Tim; Xiao, Dong; Hensley, Lisa E.; Prabakaran, Ponraj; Rockx, Barry; Sidorov, Igor A.; Corti, Oavide; Vogel, Leatrice; Feng, Yang; Kim, Jae Ouk; Wang, Lin Fa; Baric, Ralph; Lanzavecchia, Antonio; Curtis, Kristopher M.; Nabel, Gary J.; Subbarao, Kanta; Jiang, Shibo; Dimitrov, Dimiter S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 29, 17.07.2007, p. 12123-12128.

Research output: Contribution to journalArticle

Zhu, Z, Chakraborti, S, He, Y, Roberts, A, Sheahan, T, Xiao, D, Hensley, LE, Prabakaran, P, Rockx, B, Sidorov, IA, Corti, O, Vogel, L, Feng, Y, Kim, JO, Wang, LF, Baric, R, Lanzavecchia, A, Curtis, KM, Nabel, GJ, Subbarao, K, Jiang, S & Dimitrov, DS 2007, 'Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 29, pp. 12123-12128. https://doi.org/10.1073/pnas.0701000104
Zhu, Zhongyu ; Chakraborti, Samitabh ; He, Yuxian ; Roberts, Anjeanette ; Sheahan, Tim ; Xiao, Dong ; Hensley, Lisa E. ; Prabakaran, Ponraj ; Rockx, Barry ; Sidorov, Igor A. ; Corti, Oavide ; Vogel, Leatrice ; Feng, Yang ; Kim, Jae Ouk ; Wang, Lin Fa ; Baric, Ralph ; Lanzavecchia, Antonio ; Curtis, Kristopher M. ; Nabel, Gary J. ; Subbarao, Kanta ; Jiang, Shibo ; Dimitrov, Dimiter S. / Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 29. pp. 12123-12128.
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AU - Xiao, Dong

AU - Hensley, Lisa E.

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AU - Corti, Oavide

AU - Vogel, Leatrice

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AU - Curtis, Kristopher M.

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AU - Dimitrov, Dimiter S.

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