Efficacy of postinfection treatment with anti-Shiga toxin (Stx) 2 humanized monoclonal antibody TMA-15 in mice lethally challenged with Stx-producing Escherichia coli.
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.
Yamagami
S
S
Teijin Institute for Bio-Medical Research, Teijin Ltd., Tokyo 191-8512, Japan. s.yamagami@teijin.co.jp
Motoki
M
M
Kimura
T
T
Izumi
H
H
Takeda
T
T
Katsuura
Y
Y
Matsumoto
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D022641:Shiga Toxin 2 / Q000276:immunology*; D015996:Survival Rate; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D022641:Shiga Toxin 2; C437063:urtoxazumab