Generation and characterization of typhoid toxin-neutralizing human monoclonal antibodies

AUTHORS

Xuyao JiaoSarah SmithGabrielle StackQi LiangAllan BradleyPaul KellamJorge E Galán

ABSTRACT

Typhoid toxin is a virulence factor of Salmonella Typhi, the causative agent of typhoid fever, and 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 deoxyribonuclease 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 bases for the development of novel therapeutic strategies against typhoid fever.

Click here to read the article, published in the American Society for Microbiology.