High throughput discovery of influenza virus neutralizing antibodies from phage-displayed synthetic antibody libraries

Scientific Reports
Ing-Chien ChenAn-Suei Yang

Abstract

Pandemic and epidemic outbreaks of influenza A virus (IAV) infection pose severe challenges to human society. Passive immunotherapy with recombinant neutralizing antibodies can potentially mitigate the threats of IAV infection. With a high throughput neutralizing antibody discovery platform, we produced artificial anti-hemagglutinin (HA) IAV-neutralizing IgGs from phage-displayed synthetic scFv libraries without necessitating prior memory of antibody-antigen interactions or relying on affinity maturation essential for in vivo immune systems to generate highly specific neutralizing antibodies. At least two thirds of the epitope groups of the artificial anti-HA antibodies resemble those of natural protective anti-HA antibodies, providing alternatives to neutralizing antibodies from natural antibody repertoires. With continuing advancement in designing and constructing synthetic scFv libraries, this technological platform is useful in mitigating not only the threats of IAV pandemics but also those from other newly emerging viral infections.

References

Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jun 5, 2007·Vaccine·Noelle-Angelique M MolinariCarolyn B Bridges
Sep 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ming-Wei ChenDavid D Ho
Feb 24, 2009·Nature Structural & Molecular Biology·Jianhua SuiWayne A Marasco
Mar 3, 2009·Science·Damian C EkiertIan A Wilson
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Jul 9, 2011·Science·Damian C EkiertJaap Goudsmit
May 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Gui-Mei LiRafi Ahmed
Aug 11, 2012·Science·Cyrille DreyfusRobert H E Friesen
Jan 22, 2013·Annual Review of Immunology·Davide Corti, Antonio Lanzavecchia
Apr 16, 2013·Antiviral Research·Nick S Laursen, Ian A Wilson
Jun 27, 2013·Medicinal Research Reviews·Evelien Vanderlinden, Lieve Naesens
Jul 5, 2013·Nature·Jianfang ZhouYuelong Shu
Jul 28, 2013·Advances in Pharmacology·Erhard van der VriesAlbert Osterhaus
Jul 20, 2014·Current Topics in Microbiology and Immunology·Peter S Lee, Ian A Wilson
Oct 11, 2014·Expert Review of Anti-infective Therapy·Nick SpanakisAthanassios Tsakris
Oct 21, 2014·Influenza Research and Treatment·Cassandra M BerryMark Y Sangster
Feb 28, 2015·Nature Reviews. Drug Discovery·Florian Krammer, Peter Palese
Apr 8, 2015·Current Opinion in Virology·Gillian M Air
Jul 29, 2015·Frontiers in Immunology·Zachary ShriverRam Sasisekharan
Sep 8, 2015·Vaccines·Lidewij C M WiersmaRory D de Vries
Sep 8, 2015·Vaccines·Claudia TrombettaEmanuele Montomoli
Apr 1, 2016·Current Opinion in Virology·Alice Cho, Jens Wrammert
Apr 3, 2016·Vaccine·Francesco Berlanda ScorzaJohn J Donnelly
May 1, 2016·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·R D de VriesG F Rimmelzwaan
May 19, 2016·Emerging Infectious Diseases·Aeron C Hurt, Heath Kelly
Oct 30, 2016·Current Opinion in Immunology·Karlynn E NeuPatrick C Wilson
Jul 5, 2016·Nature Reviews. Immunology·Richard A Lerner
Oct 21, 2016·Current Opinion in Pharmacology·Lieve NaesensEvelien Vanderlinden
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Mar 16, 2019·Scientific Reports·Cheng-Chung LeeAndrew H-J Wang
Jan 3, 2020·Journal of Biomedical Science·Ruei-Min LuHan-Chung Wu
Jun 2, 2021·The Journal of Clinical Investigation·Tsung-Yu TsaiShie-Liang Hsieh

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Methods Mentioned

BETA
phage display
ELISA
flow cytometry
electron microscopy
PCR
column chromatography
size exclusion chromatography
transfection
FACS

Software Mentioned

Prism
R
Coot
REFMAC5
ED50 Plus
gplots
CCP4 suite
HKL
MOLREP
2000

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