Key Words

Pseudomonas exotoxin A (PE) is one of the most potent cytotoxic agents produced by Pseudomonas aeruginosa. In this study, we examined the possibility of using PE with a deletion of 38 carboxyl-terminal amino acid resi-dues, designated PE(¢576–613), for active immunization against PE-mediated disease. We first examined the toxic effects of PE and PE(¢576–613) on 5- and 9-week-old ICR mice. The results show that the subcutaneous administration of PE(¢576–613) at a dose of 250 Ìg was still nontoxic to 5- and 9-week-old ICR mice, while native PE was lethal at a dose of 0.5 and 1 Ìg, respectively. PE(¢576–613) was then used to immunize ICR mice. The minimum dose of PE(¢576–613) that could effectively induce anti-PE antibodies in 5- and 9-week-old ICR mice was found to be 250 ng. However, immunization with 250 ng PE(¢576–613) failed to protect the immunized mice from a lethal dose of PE. The effective immuniza-tion dose of PE(¢576–613) that could protect mice against a 2 Ìg PE challenge was found to be 15 Ìg. In addition, sera obtained from PE(¢576–613)-immunized ICR mice were able to neutralize PE intoxication and effectively protect mice from PE. Thus, PE(¢576–613) may be used as an alternative route to new PE vaccine development