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 languageEnglish
Pages (from-to)6-13
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number1
Early online date05 Oct 2015
DOIs
Publication statusPublished - Jan 2016

Keywords

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

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    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