EurekaMag
+ Translate
+ Most Popular
The pigeon tick (Argas reflexus): its biology, ecology, and epidemiological aspects
Prevalence of hemoglobin abnormalities in Kebili (Tunisian South)
Lipogranuloma: a preventable complication of dacryocystorhinostomy
Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency
Bees from the Belgian Congo. The acraensis group of Anthophora
Placing gingival retraction cord
Total serum IgE, allergy skin testing, and the radioallergosorbent test for the diagnosis of allergy in asthmatic children
Acariens plumicoles Analgesoidea parasites des oiseaux du Maroc
Injuries of terminal phalanges of the fingers in children
Biology of flowering and nectar production in pear (Pyrus communis)
Das Reliktvorkommen der Aspisviper (Vipera aspis L.) im Schwarzwald
Hydrological modelling of drained blanket peatland
Pathologic morphology and clinical significance of the anomalous origin of the left circumflex coronary artery from the right coronary artery. General review and autopsy analysis of 30 cases
Cyto genetic analyses of lymphocyte cultures after exposure to calcium cyclamate
Axelrodia riesei, a new characoid fish from Upper Rio Meta in Colombia With remarks concerning the genus Axelrodia and description of a similar, sympatric, Hyphessobrycon-species
Favorable evolution of a case of tuberculosis of pancreas under antibiotic action
RIFM fragrance ingredient safety assessment, Valencene, CAS Registry Number 4630-07-3
Parenteral microemulsions: an overview
Temperate pasture: management for grazing and conservation
Evaluation of a new coprocessed compound based on lactose and maize starch for tablet formulation
Thermal expansion and cracking of three confined water-saturated igneous rocks to 800C
Revision of the genera of the tribe Stigmoderini (Coleoptera: Buprestidae) a discussion of phylogenetic relationships
Anal tuberculosis. Report of a case
Gastric tuberculosis in the past and present
Adaptive responses of the cardiovascular system to prolonged spaceflight conditions: assessment with Holter monitoring

Trivalency of a Nanobody Specific for the Human Respiratory Syncytial Virus Fusion Glycoprotein Drastically Enhances Virus Neutralization and Impacts Escape Mutant Selection


Trivalency of a Nanobody Specific for the Human Respiratory Syncytial Virus Fusion Glycoprotein Drastically Enhances Virus Neutralization and Impacts Escape Mutant Selection



Antimicrobial Agents and ChemoTherapy 60(11): 6498-6509



ISSN/ISBN: 0066-4804

PMID: 27550346

DOI: 10.1128/aac.00842-16

ALX-0171 is a trivalent Nanobody derived from monovalent Nb017 that binds to antigenic site II of the human respiratory syncytial virus (hRSV) fusion (F) glycoprotein. ALX-0171 is about 6,000 to 10,000 times more potent than Nb017 in neutralization tests with strains of hRSV antigenic groups A and B. To explore the effect of this enhanced neutralization on escape mutant selection, viruses resistant to either ALX-0171 or Nb017 were isolated after serial passage of the hRSV Long strain in the presence of suboptimal concentrations of the respective Nanobodies. Resistant viruses emerged notably faster with Nb017 than with ALX-0171 and in both cases contained amino acid changes in antigenic site II of hRSV F. Detailed binding and neutralization analyses of these escape mutants as well as previously described mutants resistant to certain monoclonal antibodies (MAbs) offered a comprehensive description of site II mutations which are relevant for neutralization by MAbs and Nanobodies. Notably, ALX-0171 showed a sizeable neutralization potency with most escape mutants, even with some of those selected with the Nanobody, and these findings make ALX-0171 an attractive antiviral for treatment of hRSV infections.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 059175156

Download citation: RISBibTeXText

Related references

Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein. Virology 454-455: 139-144, 2014

Respiratory syncytial virus fusion glycoprotein: further characterization of a major epitope involved in virus neutralization. Canadian Journal of Microbiology 33(10): 933-938, 1987

Neutralization of human respiratory syncytial virus infectivity by antibodies and low-molecular-weight compounds targeted against the fusion glycoprotein. Journal of Virology 84(16): 7970-7982, 2010

Neutralization epitopes of the F glycoprotein of respiratory syncytial virus: effect of mutation upon fusion function. Journal of Virology 63(7): 2941-2950, 1989

Prevalence and Significance of Substitutions in the Fusion Protein of Respiratory Syncytial Virus Resulting in Neutralization Escape From Antibody MEDI8897. Journal of Infectious Diseases 218(4): 572-580, 2018

An investigation of the genetic basis of increased susceptibility to neutralization by anti-fusion glycoprotein antibody arising on passage of human respiratory syncytial virus in cell culture. Journal of Medical Virology 87(1): 130-140, 2015

Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation. Virology 460-461: 119-127, 2014

Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein. Nature Communications 8(1): 1877, 2017

Comparison of human respiratory syncytial virus A2 and 8/60 fusion glycoprotein gene sequences and mapping of sub-group specific antibody epitopes. Journal of Medical Virology 63(2): 168-177, 2001

The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparan sulfate. Journal of Virology 74(14): 6442-6447, 2000

Murine Pneumonia Virus Expressing the Fusion Glycoprotein of Human Respiratory Syncytial Virus from an Added Gene Is Highly Attenuated and Immunogenic in Rhesus Macaques. Journal of Virology 92(17), 2018

Attenuated Human Parainfluenza Virus Type 1 Expressing the Respiratory Syncytial Virus (RSV) Fusion (F) Glycoprotein from an Added Gene: Effects of Prefusion Stabilization and Packaging of RSV F. Journal of Virology 91(22), 2017

Enhanced neutralization of human respiratory syncytial virus by mixtures of monoclonal antibodies to the attachment (G) glycoprotein. Journal of General Virology 79: 2215-2220, 1998

Deduced amino acid sequence of the fusion glycoprotein of turkey rhinotracheitis virus has greater identity with that of human respiratory syncytial virus, a pneumovirus, than that of paramyxoviruses and morbilliviruses. Journal of General Virology 72: 75-81, 1991

Evaluation of Measles Vaccine Virus as a Vector to Deliver Respiratory Syncytial Virus Fusion Protein or Epstein-Barr Virus Glycoprotein gp350. Open Virology Journal 6: 12-22, 2012