The Journal of Experimental Medicine
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Published online February 11, 2008
doi:10.1084/jem.20072208
The Journal of Experimental Medicine, Vol. 205, No. 2, 287-294
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Wardenburg et al.
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BRIEF DEFINITIVE REPORT

Vaccine protection against Staphylococcus aureus pneumonia

Juliane Bubeck Wardenburg1,2 and Olaf Schneewind1

1 Department of Microbiology and 2 Department of Pediatrics, University of Chicago, Chicago, IL 60637

CORRESPONDENCE Olaf Schneewind: oschnee{at}bsd.uchicago.edu

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 (HlaH35L), 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.



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