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 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.

• Authors: Laurent Detalle, Thomas Stohr, Concepción Palomo, Pedro A Piedra, Brian E Gilbert, Vicente Mas, Andrena Millar, Ultan F Power, Catelijne Stortelers, Koen Allosery, José A Melero, Erik Depla
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 60 Issue 1 Pg. 6-13 (01 2016) ISSN: 1098-6596 [Electronic] United States
• PMID: 26438495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Detalle et al.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Antiviral Agents
• F protein, human respiratory syncytial virus
• Recombinant Proteins
• Single-Domain Antibodies
• Viral Fusion Proteins
• Palivizumab

Topics

• Administration, Inhalation
• Animals
• Antibodies, Neutralizing (biosynthesis, immunology, pharmacology)
• Antibodies, Viral (biosynthesis, immunology, pharmacology)
• Antiviral Agents (immunology, metabolism, pharmacology)
• Female
• Gene Expression
• Humans
• Lung (drug effects, immunology, virology)
• Male
• Models, Molecular
• Nasal Cavity (drug effects, immunology, virology)
• Neutralization Tests
• Palivizumab (biosynthesis, immunology, pharmacology)
• Pichia (genetics, metabolism)
• Rats
• Recombinant Proteins (chemistry, genetics, immunology)
• Respiratory Syncytial Virus Infections (drug therapy, immunology, pathology, virology)
• Respiratory Syncytial Viruses (drug effects, immunology, pathogenicity)
• Sigmodontinae
• Single-Domain Antibodies (biosynthesis, immunology, pharmacology)
• Viral Fusion Proteins (antagonists & inhibitors, chemistry, genetics, immunology)
• Viral Load (drug effects)
• Virus Replication (drug effects)