Open AccessGeneration and Characterization of Typhoid Toxin-Neutralizing Human Monoclonal Antibodies
Author(s) -
Xuyao Jiao,
Sarah E. Smith,
Gabrielle Stack,
Qi Liang,
Allan Bradley,
Paul Kellam,
Jorge E. Galán
Publication year - 2020
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00292-20
Subject(s) - typhoid fever , monoclonal antibody , biology , antibody , virology , toxin , salmonella typhi , virulence factor , microbiology and biotechnology , salmonella enterica , virulence , salmonella , immunology , gene , escherichia coli , bacteria , genetics
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.