Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection

Laurent Detalle; Thomas Stohr; Concepción Palomo; Pedro A. Piedra; Brian E. Gilbert; Vicente  Mas; Andrena Millar; Ultan F. Power; Catelijne  Stortelers; Koen  Allosery; Jose A. Melero; Erik  Depla

doi:doi:10.1128/AAC.01802-15

Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection

Laurent Detalle, Thomas Stohr, Concepción Palomo, Pedro A. Piedra, Brian E. Gilbert, Vicente Mas, Andrena Millar, Ultan F. Power, Catelijne Stortelers, Koen Allosery, Jose A. Melero, Erik Depla

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Abstract

Respiratory Syncytial Virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanised monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F-protein with subnanomolar affinity. ALX-0171 demonstrated superior in vitro neutralisation compared to palivizumab against prototypic RSV A and B strains. Moreover, ALX-0171 completely blocked replication below limit of detection in 87% of the viruses tested versus 18% for palivizumab at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease.

Original language	English
Pages (from-to)	6-13
Number of pages	8
Journal	Antimicrobial Agents and Chemotherapy
Volume	60
Issue number	1
Early online date	05 Oct 2015
DOIs	https://doi.org/doi:10.1128/AAC.01802-15
Publication status	Published - Jan 2016

Keywords

RSV
Nanobody
Bronchiolitis,
Nebulisation
Virology
Lower respiratory tract infections
F-protein

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doi:10.1128/AAC.01802-15

Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection
Copyright © 2015 Detalle et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license,(https://creativecommons.org/licenses/by-sa/3.0/), which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
Final published version, 1.03 MB

Ultan Power
- u.powerqub.acuk
- School of Medicine, Dentistry and Biomedical Sciences - Professor
- Wellcome Wolfson Institute for Experimental Medicine
Person: Academic

Cite this

Detalle, L., Stohr, T., Palomo, C., Piedra, P. A., Gilbert, B. E., Mas, V., Millar, A., Power, U. F., Stortelers, C., Allosery, K., Melero, J. A., & Depla, E. (2016). Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection. Antimicrobial Agents and Chemotherapy, 60(1), 6-13. https://doi.org/doi:10.1128/AAC.01802-15

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title = "Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection",

abstract = "Respiratory Syncytial Virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanised monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F-protein with subnanomolar affinity. ALX-0171 demonstrated superior in vitro neutralisation compared to palivizumab against prototypic RSV A and B strains. Moreover, ALX-0171 completely blocked replication below limit of detection in 87% of the viruses tested versus 18% for palivizumab at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease.",

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author = "Laurent Detalle and Thomas Stohr and Concepci{\'o}n Palomo and Piedra, {Pedro A.} and Gilbert, {Brian E.} and Vicente Mas and Andrena Millar and Power, {Ultan F.} and Catelijne Stortelers and Koen Allosery and Melero, {Jose A.} and Erik Depla",

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Detalle, L, Stohr, T, Palomo, C, Piedra, PA, Gilbert, BE, Mas, V, Millar, A, Power, UF, Stortelers, C, Allosery, K, Melero, JA & Depla, E 2016, 'Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection', Antimicrobial Agents and Chemotherapy, vol. 60, no. 1, pp. 6-13. https://doi.org/doi:10.1128/AAC.01802-15

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AU - Detalle, Laurent

AU - Stohr, Thomas

AU - Palomo, Concepción

AU - Piedra, Pedro A.

AU - Gilbert, Brian E.

AU - Mas, Vicente

AU - Millar, Andrena

AU - Power, Ultan F.

AU - Stortelers, Catelijne

AU - Allosery, Koen

AU - Melero, Jose A.

AU - Depla, Erik

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N2 - Respiratory Syncytial Virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanised monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F-protein with subnanomolar affinity. ALX-0171 demonstrated superior in vitro neutralisation compared to palivizumab against prototypic RSV A and B strains. Moreover, ALX-0171 completely blocked replication below limit of detection in 87% of the viruses tested versus 18% for palivizumab at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease.

AB - Respiratory Syncytial Virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanised monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F-protein with subnanomolar affinity. ALX-0171 demonstrated superior in vitro neutralisation compared to palivizumab against prototypic RSV A and B strains. Moreover, ALX-0171 completely blocked replication below limit of detection in 87% of the viruses tested versus 18% for palivizumab at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease.

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KW - Bronchiolitis,

KW - Nebulisation

KW - Virology

KW - Lower respiratory tract infections

KW - F-protein

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DO - doi:10.1128/AAC.01802-15

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JF - Antimicrobial Agents and Chemotherapy

IS - 1

ER -

Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection

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Keywords

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