title: Vaccination with a UV-irradiated genetically attenuated mutant of Staphylococcus aureus provides protection against subsequent systemic infection.
abstract: Staphylococcus aureus are gram-positive bacteria that cause clinically significant infections in humans. Severe S. aureus infections are particularly problematic in hospitalized patients and reoccur despite therapeutic measures. The absence of natural protective immune responses and the lack of high-throughput approaches to identify S. aureus antigens have imposed constraints in the development of effective vaccines. Here, we showed that vaccination with the genetically attenuated S. aureus mutant, inactivated using UV irradiation rather than heat, significantly increased survival and diminished bacterial burden and kidney abscesses when mice were challenged with virulent methicillin-sensitive or methicillin-resistant S. aureus. Protection conferred by immunization could be transferred to the naive host and was not observed in B-cell-deficient mice. Using a novel S. aureus whole-proteome microarray, we show that immunoglobulin G antibody responses to 83 proteins were observed in the immunized mice. These results suggest that protection against S. aureus infections requires antibody responses to the wide repertoire of antigens/virulence factors. Vaccination using UV-irradiated genetically attenuated S. aureus induces humoral immunity and provides a vaccine strategy for pathogens that fail to induce protective immunity. We also describe a novel, high-throughput technology to easily identify S. aureus antigens for vaccine development.
authors.affiliation: Seattle Children's Research Institute, University of Washington School of Medicine, Seattle, WA 98101-1304, USA.
authors.forename: Kellie
authors.initials: K
authors.lastname: Burnside
authors.forename: Annalisa
authors.initials: A
authors.lastname: Lembo
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Harrell
authors.forename: Jessica Abbey
authors.initials: JA
authors.lastname: Klein
authors.forename: Jesus
authors.initials: J
authors.lastname: Lopez-Guisa
authors.forename: Amy M
authors.initials: AM
authors.lastname: Siegesmund
authors.forename: Troy R
authors.initials: TR
authors.lastname: Torgerson
authors.forename: Mohamed
authors.initials: M
authors.lastname: Oukka
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Molina
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rajagopal
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism; D001402:B-Lymphocytes; D001426:Bacterial Proteins / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000276:immunology*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014774:Virulence
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D015850:Interleukin-6; D013209:Staphylococcal Vaccines