A haemagglutinin (HA1)-specific FAb neutralizes influenza A virus by inhibiting fusion activity.
H9-D3-4R2 (referred to as H9), a murine monoclonal HA1-specific IgG3, recognizes an epitope within antigenic site Cb of influenza virus A/PR/8/34 (H1N1). At 50% neutralization, inhibition of virus-mediated fusion was responsible for the majority of neutralization but, at higher antibody concentrations, the attachment of virus to target cells was also inhibited and may have contributed to neutralization. H9 FAb was also neutralizing, although the concentration needed was two orders of magnitude greater than for the IgG. Functional affinity of the IgG and affinity of the FAb were almost identical, and it is not clear why the neutralization efficiency of the FAb was so low. Unlike its IgG, H9 FAb had no detectable effect on virus attachment but inhibited virus fusion activity. It thus appears that monovalent binding by this antibody is sufficient to inhibit fusion activity and that this was directly responsible for neutralization of infectivity.
Edwards
M J
MJ
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK1.
Dimmock
N J
NJ
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK1.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D000914:Antibodies, Viral / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D000915:Antibody Affinity; D001666:Binding Sites, Antibody; D002460:Cell Line; D004285:Dogs; D004306:Dose-Response Relationship, Immunologic; D004705:Endocytosis / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006386:Hemagglutination Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology* / Q000378:metabolism*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology* / Q000494:pharmacology; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D007700:Kinetics; D008561:Membrane Fusion / Q000187:drug effects; D008958:Models, Molecular; D009500:Neutralization Tests; D011487:Protein Conformation; D020349:Surface Plasmon Resonance; D013816:Thermodynamics
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G