Vaccine protection against Staphylococcus aureus pneumonia.
Staphylococcus aureus pneumonia causes significant mortality in hospitalized or healthy individuals, and recent increases in morbidity are attributed to the rapid spread of methicillin-resistant S. aureus (MRSA) strains, which are often not susceptible to antibiotic therapy. Alpha-hemolysin (Hla), a secreted pore-forming toxin, is an essential virulence factor of MRSA in a mouse model of S. aureus pneumonia. We show that the level of Hla expression by independent S. aureus strains directly correlates with their virulence. Active immunization with a mutant form of Hla (Hla(H35L)), which cannot form pores, generates antigen-specific immunoglobulin G responses and affords protection against staphylococcal pneumonia. Moreover, transfer of Hla-specific antibodies protects naive animals against S. aureus challenge and prevents the injury of human lung epithelial cells during infection. Thus, Hla vaccination or immunotherapy may prevent S. aureus pneumonia in humans.
Bubeck Wardenburg
Juliane
J
Department of Microbiology, University of Chicago, Chicago, IL 60637, USA.
Schneewind
Olaf
O
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000097:blood; D006460:Hemolysin Proteins / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D008810:Mice, Inbred C57BL; D011023:Pneumonia, Staphylococcal / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D013209:Staphylococcal Vaccines; D013211:Staphylococcus aureus / Q000276:immunology*; D014611:Vaccination
D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D006460:Hemolysin Proteins; D013209:Staphylococcal Vaccines; C021091:staphylococcal alpha-toxin