A nontoxicPseudomonas exotoxin a induces active immunity and passive protective antibody againstPseudomonas exotoxin a intoxication

Abstract

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(Delta576-613), for active immunization against PE-mediated disease. We first examined the toxic effects of PE and PE(Delta576-613) on 5- and 9-week-old ICR mice. The results show that the subcutaneous administration of PE(Delta576-613) at a dose of 250 microg was still nontoxic to 5- and 9-week-old ICR mice, while native PE was lethal at a dose of 0.5 and 1 microg, respectively. PE(Delta576-613) was then used to immunize ICR mice. The minimum dose of PE(Delta576-613) 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(Delta576-613) failed to protect the immunized mice from a lethal dose of PE. The effective immunization dose of PE(Delta576-613) that could protect mice against a 2 microg PE challenge was found to be 15 microg. In addition, sera obtained from PE(Delta576-613)-immunized ICR mice were able to neutralize PE intoxication and effectively protect mice from PE. Thus, PE(Delta576-613) may be used as an alternative route to new PE vaccine development.

Protective Effect of DNA Vaccine Encoding Pseudomonas Exotoxin A and PcrV against Acute Pulmonary P. aeruginosa Infection

“…It’s revealed that P. aeruginosa possesses various protein secretion systems to invade and damage host cells, of which the type II secretion system (T2SS) and type III secretion system (T3SS) secrete the majority of known toxins [23], [56], [57]. As an important cytotoxic extracellular protein, Exotoxin A also acquires effective immunogenicity, making it potential candidate for Pseudomonas vaccine [58]–[60]. PcrV is a key component of T3SS, regulating the assembly of virulence effector-delivery structure in eukaryotic cell membrane, besides, efficacy of anti-PcrV immunotherapy in animal of P. aeruginosa infection suggested the immune-protective feasibility of PcrV [36], [61].…”