Target-Agnostic Identification of Functional Monoclonal Antibodies Against Klebsiella pneumoniae Multimeric MrkA Fimbrial Subunit

The Journal of Infectious Diseases
Qun WangXiaodong Xiao

Abstract

The increasing incidence of Klebsiella pneumoniae infections refractory to treatment with current broad-spectrum antibiotic classes warrants the exploration of alternative approaches, such as antibody therapy and/or vaccines, for prevention and treatment. However, the lack of validated targets shared by spectrums of clinical strains poses a significant challenge. We adopted a target-agnostic approach to identify protective antibodies against K. pneumoniae Several monoclonal antibodies were isolated from phage display and hybridoma platforms by functional screening for opsonophagocytic killing activity. We further identified their common target antigen to be MrkA, a major protein in the type III fimbriae complex, and showed that these serotype-independent anti-MrkA antibodies reduced biofilm formation in vitro and conferred protection in multiple murine pneumonia models. Importantly, mice immunized with purified MrkA proteins also showed reduced bacterial burden following K. pneumoniae challenge. Taken together, these results support MrkA as a promising target for K. pneumoniae antibody therapeutics and vaccines.

References

Feb 1, 1984·The Journal of Infectious Diseases·A S CrossI Orskov
Jul 1, 1996·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·W N CampbellA S Cross
Jul 29, 2005·International Journal of Medical Microbiology : IJMM·Heather LavenderSteven Clegg
Nov 22, 2011·Vaccine·Tarek A AhmadEl Sayed H El Ashry
Jun 27, 2012·The Journal of Experimental Medicine·Antonio DiGiandomenicoC Kendall Stover
Aug 24, 2012·Future Microbiology·Caitlin N Murphy, Steven Clegg
Aug 24, 2012·Science Translational Medicine·Evan S SnitkinJulia A Segre
Dec 20, 2012·Human Vaccines & Immunotherapeutics·Urban LundbergMarkus Hanner
Jul 28, 2013·Nature·Maryn McKenna
Aug 24, 2013·The Lancet Infectious Diseases·L Silvia Munoz-PriceJohn P Quinn
Aug 27, 2013·Virulence·Alan S Cross
Nov 13, 2013·Expert Opinion on Investigational Drugs·Ze-Qi XuJohn Flavin
Feb 25, 2014·Chemistry & Biology·John McCafferty
Aug 29, 2014·F1000prime Reports·Christopher A BrobergVirginia L Miller
Nov 14, 2014·Science Translational Medicine·Antonio DiGiandomenicoC Kendall Stover
Sep 18, 2015·Archives of Microbiology·Priya GuptaProsun Tribedi

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Citations

Jul 20, 2016·Human Vaccines & Immunotherapeutics·Xiaodong XiaoWilliam F Dall'Acqua
Jan 20, 2017·MAbs·Qun WangXiaodong Xiao
Mar 11, 2020·Antimicrobial Agents and Chemotherapy·Omari Jones-NelsonBret R Sellman
Jun 5, 2020·Future Microbiology·Juliana C de M CamposRosana Br Ferreira
Mar 25, 2017·Nature Reviews. Drug Discovery·Seth W DickeyMichael Otto
Aug 16, 2018·American Journal of Respiratory Cell and Molecular Biology·Omari Jones-NelsonBret R Sellman
Jul 10, 2020·Proceedings of the National Academy of Sciences of the United States of America·Eva GatoAstrid Pérez
Nov 1, 2017·Frontiers in Microbiology·Tien-Huang LinChing-Ting Lin
Dec 9, 2020·FEMS Microbiology Reviews·Mireia López-SilesMichael J McConnell
Jun 19, 2018·Current Opinion in Chemical Engineering·Ellen K Wagner, Jennifer A Maynard
May 1, 2021·International Journal of Molecular Sciences·Vanessa AratoFrancesca Micoli
May 1, 2021·Frontiers in Medicine·Vitali SintchenkoBen Marais
Oct 2, 2019·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·J VilaC Ballesté-Delpierre
May 7, 2021·FEMS Microbiology Reviews·Mireia López-SilesMichael J McConnell
Jul 27, 2021·Frontiers in Cellular and Infection Microbiology·Kristian Daniel Ralph RothMichael Hust
Jul 21, 2017·Chemical Reviews·Mingying YangChuanbin Mao
Sep 4, 2021·Infectious Diseases and Therapy·Lucas AssoniMichelle Darrieux

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