A live-attenuated Pseudomonas aeruginosa vaccine elicits outer membrane protein-specific active and passive protection against corneal infection.
Pseudomonas aeruginosa can cause sight-threatening corneal infections in humans, particularly those who wear contact lenses. We have previously shown that a live-attenuated P. aeruginosa vaccine given intranasally protected mice against acute lethal pneumonia in a lipopolysaccharide (LPS) serogroup-specific manner. In the current study, we evaluated the protective and therapeutic efficacies, as well as the target antigens, of this vaccine in a murine corneal infection model. C3H/HeN mice were nasally immunized with the vaccine (an aroA deletion mutant of strain PAO1, designated PAO1DeltaaroA) or with Escherichia coli as a control and were challenged 3 weeks later by inoculating the scratch-injured cornea with P. aeruginosa. For passive prophylaxis and therapy, we utilized a serum raised in rabbits nasally immunized with PAO1DeltaaroA or E. coli. Outcome measures included corneal pathology scores and, in some experiments, reductions in total and internalized bacterial CFU. We found that both active and passive immunization reduced corneal pathology scores after challenge with a variety of P. aeruginosa strains, including several serogroup-heterologous strains. Even when given therapeutically starting as late as 24 h after infection, the rabbit antiserum to PAO1DeltaaroA was effective at reducing corneal pathology scores. Immunotherapy of established infections also reduced the numbers of total and internalized corneal P. aeruginosa bacteria. Experiments using absorbed sera showed that the protective antibodies are specific to outer membrane proteins. Thus, live-attenuated P. aeruginosa vaccines delivered nasally protect against corneal infections in mice and potentially can be used to prepare passive therapy reagents for the treatment of established P. aeruginosa corneal infections caused by diverse LPS serogroups.
Zaidi
Tanweer S
TS
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Priebe
Gregory P
GP
Pier
Gerald B
GB
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000918:Antibody Specificity; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015818:Eye Infections, Bacterial / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D007116:Immunization, Passive; D007634:Keratitis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D011552:Pseudomonas Infections / Q000276:immunology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011817:Rabbits; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology*
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007106:Immune Sera; D014613:Vaccines, Attenuated