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Molecular Pathogenesis

Generation and Characterization of Typhoid Toxin-Neutralizing Human Monoclonal Antibodies

Xuyao Jiao, Sarah Smith, Gabrielle Stack, Qi Liang, Allan Bradley, Paul Kellam, Jorge E. Galán
Victor J. Torres, Editor
Xuyao Jiao
aDepartment of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut, USA
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Sarah Smith
bKymab Ltd., Babraham Research Campus, Cambridge, United Kingdom
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Gabrielle Stack
aDepartment of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut, USA
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Qi Liang
bKymab Ltd., Babraham Research Campus, Cambridge, United Kingdom
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Allan Bradley
bKymab Ltd., Babraham Research Campus, Cambridge, United Kingdom
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Paul Kellam
bKymab Ltd., Babraham Research Campus, Cambridge, United Kingdom
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Jorge E. Galán
aDepartment of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut, USA
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  • ORCID record for Jorge E. Galán
Victor J. Torres
New York University School of Medicine
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DOI: 10.1128/IAI.00292-20
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ABSTRACT

Typhoid toxin is a virulence factor of Salmonella enterica serovar Typhi, the causative agent of typhoid fever, and is thought to be responsible for the symptoms of severe disease. This toxin has a unique A2B5 architecture with two active subunits, the ADP ribosyl transferase PltA and the DNase CdtB, linked to a pentameric B subunit, which is alternatively made of PltB or PltC. Here, we describe the generation and characterization of typhoid toxin-neutralizing human monoclonal antibodies by immunizing genetically engineered mice that have a full set of human immunoglobulin variable region genes. We identified several monoclonal antibodies with strong in vitro and in vivo toxin-neutralizing activity and different mechanisms of toxin neutralization. These antibodies could serve as the basis for the development of novel therapeutic strategies against typhoid fever.

FOOTNOTES

    • Received 14 May 2020.
    • Returned for modification 19 June 2020.
    • Accepted 6 July 2020.
    • Accepted manuscript posted online 13 July 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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Generation and Characterization of Typhoid Toxin-Neutralizing Human Monoclonal Antibodies
Xuyao Jiao, Sarah Smith, Gabrielle Stack, Qi Liang, Allan Bradley, Paul Kellam, Jorge E. Galán
Infection and Immunity Sep 2020, 88 (10) e00292-20; DOI: 10.1128/IAI.00292-20

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Generation and Characterization of Typhoid Toxin-Neutralizing Human Monoclonal Antibodies
Xuyao Jiao, Sarah Smith, Gabrielle Stack, Qi Liang, Allan Bradley, Paul Kellam, Jorge E. Galán
Infection and Immunity Sep 2020, 88 (10) e00292-20; DOI: 10.1128/IAI.00292-20
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KEYWORDS

typhoid fever
bacterial pathogenesis
Salmonella typhi
Salmonella Paratyphi
infectious diseases
bacterial toxins
monoclonal antibodies
therapeutics

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