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

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

  • Antimicrob Agents Chemother. 2015 Oct 5;60(1):6-13. doi: 10.1128/AAC.01802-15.
Laurent Detalle 1,  Thomas Stohr 2,  Concepción Palomo 3,  Pedro A Piedra 4,  Brian E Gilbert 5,  Vicente Mas 3,  Andrena Millar 6,  Ultan F Power 6,  Catelijne Stortelers 2,  Koen Allosery 2,  José A Melero 3,  Erik Depla 2
Affiliations

Affiliations

  • 1 Ablynx nv, Zwijnaarde, Belgium Laurent.detalle@ablynx.com.
  • 2 Ablynx nv, Zwijnaarde, Belgium.
  • 3 Centro Nacional de Microbiología and CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
  • 4 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
  • 5 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
  • 6 Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
PMID: 26438495 DOI: 10.1128/AAC.01802-15
Abstract

Respiratory syncytial virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly individuals. Its fusion (F) protein is critical for virus Infection. It is targeted by several investigational antivirals and by palivizumab, a humanized 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 in vitro neutralization superior to that of palivizumab against prototypic RSV subtype A and B strains. Moreover, ALX-0171 completely blocked replication to below the limit of detection for 87% of the viruses tested, whereas palivizumab did so for 18% of the viruses tested 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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