A nontoxic Pseudomonas exotoxin A induces active immunity and passive protective antibody against Pseudomonas exotoxin A intoxication

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 residues, designated PE(ΔA576-613), for active immunization against PE- mediated disease. We first examined the toxic effects of PE and PE(Δ576-613) on 5- and 9-week-old ICR mice. The results show that the subcutaneous administration of PE(Δ576-613) at a dose of 250 μg was still nontoxic to 5- and 9-week-old ICR mice, while native PE was lethal at a dose of 0.5 and 1 μg, respectively. PE(Δ576-613) was then used to immunize ICR mice. The minimum dose of PE(Δ576-613) 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(Δ576-613) failed to protect the immunized mice from a lethal dose of PE. The effective immunization dose of PE(Δ576-613) that could protect mice against a 2 μg PE challenge was found to be 15 μg. In addition, sera obtained from PE(Δ576-613)-immunized ICR mice were able to neutralize PE intoxication and effectively protect mice from PE. Thus, PE(Δ576-613) may be used as an alternative route to new PE vaccine development.