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Efficacy of Postinfection Treatment with Anti–Shiga Toxin (Stx) 2 Humanized Monoclonal Antibody TMA‐15 in Mice Lethally Challenged with Stx‐ProducingEscherichia coli
Author(s) -
Shinsuke Yamagami,
Masamichi Motoki,
Tsuyoshi Kimura,
Hiroyuki Izumi,
Tae Takeda,
Yasuhiro Katsuura,
Yohichi Matsumoto
Publication year - 2001
Publication title -
the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1086/323082
Subject(s) - shiga toxin , stx2 , microbiology and biotechnology , escherichia coli , toxin , monoclonal antibody , virulence , shiga like toxin , antibody , biology , virology , virulence factor , immunology , biochemistry , gene
Infection with Shiga toxin (Stx)-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic uremic syndrome. TMA-15 is a humanized monoclonal antibody against Stx2, a major pathogenic factor. In a mouse infection model that used B2F1, a virulent STEC strain, the efficacy of TMA-15 was assessed when it was administered after bacterial and toxin exposure. In this model, a time-course analysis of the serum Stx2 level showed that the toxin was detectable from 24 h after infection. In an evaluation of the time-dependent efficacy, treatment with TMA-15 up to 24 h after infection ameliorated the lethal challenge, although treatment at 48 h showed no efficacy. To determine the effective dose, escalating doses were administered at 24 h after infection. The number of mice that survived after doses of 0, 0.25, 0.5, 1.0, and 2.0 mg/kg were 0/20, 11/20, 17/20, 20/20, and 20/20, respectively. These findings suggest that TMA-15 shows potential for prevention of severe complications associated with STEC infection.

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