title: Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies.
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.
authors.affiliation: Protein Interactions Group, Center for Cancer Research Nanobiology Program, SAIC-Frederick, Inc., National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Samitabh
authors.initials: S
authors.lastname: Chakraborti
authors.forename: Yuxian
authors.initials: Y
authors.lastname: He
authors.forename: Anjeanette
authors.initials: A
authors.lastname: Roberts
authors.forename: Tim
authors.initials: T
authors.lastname: Sheahan
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xiao
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.forename: Ponraj
authors.initials: P
authors.lastname: Prabakaran
authors.forename: Barry
authors.initials: B
authors.lastname: Rockx
authors.forename: Igor A
authors.initials: IA
authors.lastname: Sidorov
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.forename: Leatrice
authors.initials: L
authors.lastname: Vogel
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.forename: Jae-Ouk
authors.initials: JO
authors.lastname: Kim
authors.forename: Lin-Fa
authors.initials: LF
authors.lastname: Wang
authors.forename: Ralph
authors.initials: R
authors.lastname: Baric
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.forename: Kristopher M
authors.initials: KM
authors.lastname: Curtis
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001667:Binding, Competitive; D002459:Cell Fusion; D003429:Cross Reactions; D004195:Disease Models, Animal; D004196:Disease Outbreaks; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D016296:Mutagenesis; D053827:Nandiniidae / Q000821:virology; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology* / Q000302:isolation & purification* / Q000502:physiology; D045169:Severe Acute Respiratory Syndrome / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D014764:Viral Proteins / Q000378:metabolism; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D014764:Viral Proteins