Protection against experimental Pseudomonas aeruginosa infection in mice by active immunization with exotoxin A toxoids

The immunoprophylactic effect of chemically inactivated Pseudomonas aeruginosa exotoxin A in experimental pseudomonas infections was studied. Exotoxin A toxoids were prepared by Formalin (f-TXD) or glutaraldehyde (g-TXD) treatment. Immunization of mice with three or four doses (10 micrograms each) of f-TXD and the synthetic adjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine (50 micrograms) induced high levels of antiexotoxin A antibodies as measured by passive hemagglutination assay and enzyme-linked immunosorbent assay. Immunization with toxoid alone did not elicit antitoxin. A significant increase in survival time and survival rate (P less than 0.01) was seen in immunized (f-TXD) and in burned and infected mice (50 to 85%) as compared with control mice immunized with formalinized bovine serum albumin (6 to 20%). Virtually 100% survival was obtained when preinfection immunization weas combined with single-dose gentamicin treatment within 24 h of infection. Immunization with g-TXD increased survival time (P less than 0.01) but did not consistently increase survival rate, and the results were not as satisfactory as those with formalinized exotoxin. The data presented indicate that active immunization with formalinized exotoxin A toxoid and adjuvant induced protective immunity to various degrees against infections in mice and could be potentially useful in prophylaxis of P. aeruginosa infections.