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(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.
Chen
T Y
TY
Institute of Genetics, School of Life Science, National Yang-Ming University, Taipei, Taiwan, ROC.
Lin
C P
CP
Loa
C C
CC
Chen
T L
TL
Shang
H F
HF
Hwang
J
J
Hui
C F
CF
D016475:3T3 Cells; D036002:ADP Ribose Transferases; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000633:toxicity; D001428:Bacterial Vaccines / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005098:Exotoxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000633:toxicity*; D005260:Female; D007116:Immunization, Passive; D051379:Mice; D008813:Mice, Inbred ICR; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000276:immunology / Q000506:poisoning; D017384:Sequence Deletion; D015996:Survival Rate; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D005098:Exotoxins; D010446:Peptide Fragments; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D014614:Vaccines, Synthetic; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A