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Title: Broadly-Reactive Neutralizing and Non-neutralizing Antibodies Directed against the H7 Influenza Virus Hemagglutinin Reveal Divergent Mechanisms of Protection
Authors: Tan G.S.
Leon P.E.
Albrecht R.A.
Margine I.
Hirsh A.
Bahl J. 
Krammer F.
Keywords: Fc receptor
monoclonal antibody
neutralizing antibody
virus vaccine
hemagglutinin, avian influenza A virus
influenza vaccine
Influenza virus hemagglutinin
monoclonal antibody
neutralizing antibody
virus antibody
virus antigen
animal experiment
antibody titer
antigen binding
binding kinetics
controlled study
enzyme linked immunosorbent assay
epitope mapping
flow cytometry
genetic transfection
hemagglutination inhibition
Influenza A virus (H7N9)
protein expression
protein purification
transactivation assay
Western blotting
Bagg albino mouse
disease model
Influenza A virus (H7N9)
orthomyxovirus infection
Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Antigens, Viral
Blotting, Western
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Epitope Mapping
Flow Cytometry
Hemagglutinin Glycoproteins, Influenza Virus
Influenza A Virus, H7N9 Subtype
Influenza Vaccines
Mice, Inbred BALB C
Orthomyxoviridae Infections
Issue Date: 2016
Citation: Tan G.S., Leon P.E., Albrecht R.A., Margine I., Hirsh A., Bahl J., Krammer F. (2016). Broadly-Reactive Neutralizing and Non-neutralizing Antibodies Directed against the H7 Influenza Virus Hemagglutinin Reveal Divergent Mechanisms of Protection. PLoS Pathogens 12 (4) : e1005578. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: In the early spring of 2013, Chinese health authorities reported several cases of H7N9 influenza virus infections in humans. Since then the virus has established itself at the human-animal interface in Eastern China and continues to cause several hundred infections annually. In order to characterize the antibody response to the H7N9 virus we generated several mouse monoclonal antibodies against the hemagglutinin of the A/Shanghai/1/13 (H7N9) virus. Of particular note are two monoclonal antibodies, 1B2 and 1H5, that show broad reactivity to divergent H7 hemagglutinins. Monoclonal antibody 1B2 binds to viruses of the Eurasian and North American H7 lineages and monoclonal antibody 1H5 reacts broadly to virus isolates of the Eurasian lineage. Interestingly, 1B2 shows broad hemagglutination inhibiting and neutralizing activity, while 1H5 fails to inhibit hemagglutination and demonstrates no neutralizing activity in vitro. However, both monoclonal antibodies were highly protective in an in vivo passive transfer challenge model in mice, even at low doses. Experiments using mutant antibodies that lack the ability for Fc/Fc-receptor and Fc/complement interactions suggest that the protection provided by mAb 1H5 is, at least in part, mediated by the Fc-fragment of the mAb. These findings highlight that a protective response to a pathogen may not only be due to neutralizing antibodies, but can also be the result of highly efficacious non-neutralizing antibodies not readily detected by classical in vitro neutralization or hemagglutination inhibition assays. This is of interest because H7 influenza virus vaccines induce only low hemagglutination inhibiting antibody titers while eliciting robust antibody titers as measured by ELISA. Our data suggest that these binding but non-neutralizing antibodies contribute to protection in vivo. ? 2016 Tan et al.
Source Title: PLoS Pathogens
ISSN: 15537366
DOI: 10.1371/journal.ppat.1005578
Rights: Attribution 4.0 International
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