title: Animal and human antibodies to distinct Staphylococcus aureus antigens mutually neutralize opsonic killing and protection in mice.
abstract: New prophylactic approaches are needed to control infection with the Gram-positive bacterium Staphylococcus aureus, which is a major cause of nosocomial and community-acquired infections. To develop these, greater understanding of protective immunity against S. aureus infection is needed. Human immunity to extracellular Gram-positive bacterial pathogens is primarily mediated by opsonic killing (OPK) via antibodies specific for surface polysaccharides. S. aureus expresses two such antigens, capsular polysaccharide (CP) and poly-N-acetyl glucosamine (PNAG). Here, we have shown that immunization-induced polyclonal animal antisera and monoclonal antibodies specific for either CP or PNAG antigens have excellent in vitro OPK activity in human blood but that when mixed together they show potent interference in OPK activity. In addition, reductions in antibody binding to the bacterial surface, complement deposition, and passive protection were seen in two mouse models of S. aureus infection. Electron microscopy, isothermal calorimetry, and surface plasmon resonance indicated that antibodies to CP and PNAG bound together via an apparent idiotype-anti-idiotype interaction. This interaction was also found in sera from humans with S. aureus bacteremia. These findings suggest that the lack of effective immunity to S. aureus infections in humans could be due, in part, to interference in OPK when antibodies to CP and PNAG antigens are both present. This information could be used to better design S. aureus vaccine components.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Skurnik
authors.forename: Massimo
authors.initials: M
authors.lastname: Merighi
authors.forename: Martha
authors.initials: M
authors.lastname: Grout
authors.forename: Mihaela
authors.initials: M
authors.lastname: Gadjeva
authors.forename: Tomas
authors.initials: T
authors.lastname: Maira-Litran
authors.forename: Maria
authors.initials: M
authors.lastname: Ericsson
authors.forename: Donald A
authors.initials: DA
authors.lastname: Goldmann
authors.forename: Susan S
authors.initials: SS
authors.lastname: Huang
authors.forename: Rupak
authors.initials: R
authors.lastname: Datta
authors.forename: Jean C
authors.initials: JC
authors.lastname: Lee
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
mesh_terms: D000117:Acetylglucosamine; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D003428:Cross Infection / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D009895:Opsonin Proteins / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D009895:Opsonin Proteins; C113831:poly-N-acetyl glucosamine; D000117:Acetylglucosamine