Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses

Zhi Yong Yang, Heidi C. Werner, Wing Pui Kong, Kwanyee Leung, Elisabetta Traggiai, Antonio Lanzavecchia, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

Abstract

Molecular characterization of the severe acute respiratory syndrome coronavirus has revealed genetic diversity among isolates. The spike (S) glycoprotein, the major target for vaccine and immune therapy, shows up to 17 substitutions in its 1,255-aa sequence; however, the biologic significance of these changes is unknown. Here, the functional effects of S mutations have been determined by analyzing their affinity for a viral receptor, human angiotensin-converting enzyme 2 (hACE-2), and their sensitivity to Ab neutralization with viral pseudotypes. Although minor differences among eight strains transmitted during human outbreaks in early 2003 were found, substantial functional changes were detected in S derived from a case in late 2003 from Guangdong province [S(GD03T0013)] and from two palm civets, S(SZ3) and S(SZ16). S(GD03T0013) depended less on the hACE-2 receptor and was markedly resistant to Ab inhibition. Unexpectedly, Abs that neutralized most human S glycoproteins enhanced entry mediated by the civet virus S glycoproteins. The mechanism of enhancement involved the interaction of Abs with conformational epitopes in the hACE-2-binding domain. Finally, improved immunogens and mAbs that minimize this complication have been defined. These data show that the entry of severe acute respiratory syndrome coronaviruses can be enhanced by Abs, and they underscore the need to address the evolving diversity of this newly emerged virus for vaccines and immune therapies.

Original languageEnglish (US)
Pages (from-to)797-801
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number3
DOIs
StatePublished - Jan 18 2005
Externally publishedYes

Keywords

  • Angiotensin-converting enzyme 2
  • Enhancement
  • Immunoglobulin G
  • Pseudovirus

ASJC Scopus subject areas

  • Genetics
  • General

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