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Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state

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Abstract
Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV.
Keywords
HUMANIZED MONOCLONAL-ANTIBODY, PICHIA-PASTORIS, IN-VITRO, INFECTION, GLYCOPROTEIN, MOTAVIZUMAB, SOFTWARE, RISK

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Chicago
Rossey, Iebe, Morgan SA Gilman, Stephanie C Kabeche, Koen Sedeyn, Daniel Wrapp, Masaru Kanekiyo, Man Chen, et al. 2017. “Potent Single-domain Antibodies That Arrest Respiratory Syncytial Virus Fusion Protein in Its Prefusion State.” Nature Communications 8.
APA
Rossey, I., Gilman, M. S., Kabeche, S. C., Sedeyn, K., Wrapp, D., Kanekiyo, M., Chen, M., et al. (2017). Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state. NATURE COMMUNICATIONS, 8.
Vancouver
1.
Rossey I, Gilman MS, Kabeche SC, Sedeyn K, Wrapp D, Kanekiyo M, et al. Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state. NATURE COMMUNICATIONS. 2017;8.
MLA
Rossey, Iebe, Morgan SA Gilman, Stephanie C Kabeche, et al. “Potent Single-domain Antibodies That Arrest Respiratory Syncytial Virus Fusion Protein in Its Prefusion State.” NATURE COMMUNICATIONS 8 (2017): n. pag. Print.
@article{8512252,
  abstract     = {Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV.},
  articleno    = {14158},
  author       = {Rossey, Iebe and Gilman, Morgan SA and Kabeche, Stephanie C and Sedeyn, Koen and Wrapp, Daniel and Kanekiyo, Masaru and Chen, Man and Mas, Vicente and Spitaels, Jan and Melero, José A and Graham, Barney S and Schepens, Bert and McLellan, Jason S and Saelens, Xavier},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {HUMANIZED MONOCLONAL-ANTIBODY,PICHIA-PASTORIS,IN-VITRO,INFECTION,GLYCOPROTEIN,MOTAVIZUMAB,SOFTWARE,RISK},
  language     = {eng},
  pages        = {12},
  title        = {Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state},
  url          = {http://dx.doi.org/10.1038/ncomms14158},
  volume       = {8},
  year         = {2017},
}

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