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Generation and Characterization of Typhoid Toxin-Neutralizing Human Monoclonal Antibodies.

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.

SUBMITTER: Jiao X

PROVIDER: S-EPMC7504945 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Generation and Characterization of Typhoid Toxin-Neutralizing Human Monoclonal Antibodies.

Jiao Xuyao X Smith Sarah S Stack Gabrielle G Liang Qi Q Bradley Allan A Kellam Paul P Galán Jorge E JE

Infection and immunity 20200918 10

Typhoid toxin is a virulence factor of <i>Salmonella enterica</i> 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 ...[more]

PMID: 32661121

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