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

(2011) JOURNAL OF INFECTIOUS DISEASES. 204(11). p.1692-1701
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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.
Keywords
MONOCLONAL-ANTIBODIES, REPLICATION IN-VITRO, STRUCTURAL BASIS, GLYCOPROTEIN, NEUTRALIZATION, CONFORMATION, MOTAVIZUMAB, PALIVIZUMAB, INFANTS, FORMS

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Citation

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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.
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.
Chicago author-date
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.
Chicago author-date (all authors)
Schepens, Bert, Lorena Ibanez, Sarah De Baets, Anna Hultberg, Pieter Bogaert, Pieter De Bleser, Frederik Vervalle, Theo Verrips, Jose Melero, Wesly Vandevelde, Peter Vanlandschoot, and Xavier Saelens. 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.
IEEE
[1]
B. Schepens et al., “Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion,” JOURNAL OF INFECTIOUS DISEASES, vol. 204, no. 11, pp. 1692–1701, 2011.
@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},
  keywords     = {MONOCLONAL-ANTIBODIES,REPLICATION IN-VITRO,STRUCTURAL BASIS,GLYCOPROTEIN,NEUTRALIZATION,CONFORMATION,MOTAVIZUMAB,PALIVIZUMAB,INFANTS,FORMS},
  language     = {eng},
  number       = {11},
  pages        = {1692--1701},
  title        = {Nanobodies® 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},
}

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