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Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion

Bert Schepens UGent, Lorena Ibanez UGent, Sarah De Baets UGent, Anna Hultberg, Pieter Bogaert UGent, Pieter De Bleser UGent, Frederik Vervalle UGent, Theo Verrips, Jose Melero and Wesly Vandevelde, et al. (2011) JOURNAL OF INFECTIOUS DISEASES. 204(11). p.1692-1701
abstract
Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.
Please use this url to cite or link to this publication:
author
organization
alternative title
Nanobodies (R) specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion
year
type
journalArticle (original)
publication status
published
subject
keyword
MONOCLONAL-ANTIBODIES, REPLICATION IN-VITRO, STRUCTURAL BASIS, GLYCOPROTEIN, NEUTRALIZATION, CONFORMATION, MOTAVIZUMAB, PALIVIZUMAB, INFANTS, FORMS
journal title
JOURNAL OF INFECTIOUS DISEASES
J. Infect. Dis.
volume
204
issue
11
pages
1692 - 1701
Web of Science type
Article
Web of Science id
000296297900008
JCR category
INFECTIOUS DISEASES
JCR impact factor
6.41 (2011)
JCR rank
3/70 (2011)
JCR quartile
1 (2011)
ISSN
0022-1899
DOI
10.1093/infdis/jir622
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1942045
handle
http://hdl.handle.net/1854/LU-1942045
date created
2011-11-10 15:26:35
date last changed
2012-06-26 14:32:27
@article{1942045,
  abstract     = {Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.},
  author       = {Schepens, Bert and Ibanez, Lorena and De Baets, Sarah and Hultberg, Anna and Bogaert, Pieter and De Bleser, Pieter and Vervalle, Frederik and Verrips, Theo and Melero, Jose and Vandevelde, Wesly and Vanlandschoot, Peter and Saelens, Xavier},
  issn         = {0022-1899},
  journal      = {JOURNAL OF INFECTIOUS DISEASES},
  keyword      = {MONOCLONAL-ANTIBODIES,REPLICATION IN-VITRO,STRUCTURAL BASIS,GLYCOPROTEIN,NEUTRALIZATION,CONFORMATION,MOTAVIZUMAB,PALIVIZUMAB,INFANTS,FORMS},
  language     = {eng},
  number       = {11},
  pages        = {1692--1701},
  title        = {Nanobodies{\textregistered} specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion},
  url          = {http://dx.doi.org/10.1093/infdis/jir622},
  volume       = {204},
  year         = {2011},
}

Chicago
Schepens, Bert, Lorena Ibanez, Sarah De Baets, Anna Hultberg, Pieter Bogaert, Pieter De Bleser, Frederik Vervalle, et al. 2011. “Nanobodies® Specific for Respiratory Syncytial Virus Fusion Protein Protect Against Infection by Inhibition of Fusion.” Journal of Infectious Diseases 204 (11): 1692–1701.
APA
Schepens, B., Ibanez, L., De Baets, S., Hultberg, A., Bogaert, P., De Bleser, P., Vervalle, F., et al. (2011). Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion. JOURNAL OF INFECTIOUS DISEASES, 204(11), 1692–1701.
Vancouver
1.
Schepens B, Ibanez L, De Baets S, Hultberg A, Bogaert P, De Bleser P, et al. Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion. JOURNAL OF INFECTIOUS DISEASES. 2011;204(11):1692–701.
MLA
Schepens, Bert, Lorena Ibanez, Sarah De Baets, et al. “Nanobodies® Specific for Respiratory Syncytial Virus Fusion Protein Protect Against Infection by Inhibition of Fusion.” JOURNAL OF INFECTIOUS DISEASES 204.11 (2011): 1692–1701. Print.