title: Antibodies to Staphylococcus aureus capsular polysaccharides 5 and 8 perform similarly in vitro but are functionally distinct in vivo.
abstract: The capsular polysaccharide (CP) produced by Staphylococcus aureus is a virulence factor that allows the organism to evade uptake and killing by host neutrophils. Polyclonal antibodies to the serotype 5 (CP5) and type 8 (CP8) capsular polysaccharides are opsonic and protect mice against experimental bacteremia provoked by encapsulated staphylococci. Thus, passive immunotherapy using CP antibodies has been considered for the prevention or treatment of invasive antibiotic-resistant S. aureus infections. In this report, we generated monoclonal antibodies (mAbs) against S. aureus CP5 or CP8. Backbone specific mAbs reacted with native and O-deacetylated CPs, whereas O-acetyl specific mAbs reacted only with native CPs. Reference strains of S. aureus and a selection of clinical isolates reacted by colony immunoblot with the CP5 and CP8 mAbs in a serotype-specific manner. The mAbs mediated in vitro CP type-specific opsonophagocytic killing of S. aureus strains, and mice passively immunized with CP5 mAbs were protected against S. aureus bacteremia. Neither CP8-specific mAbs or polyclonal antibodies protected mice against bacteremia provoked by serotype 8 S. aureus clinical isolates, although these same antibodies did protect against a serotype 5 S. aureus strain genetically engineered to produce CP8. We detected soluble CP8 in culture supernatants of serotype 8 clinical isolates and in the plasma of infected animals. Serotype 5 S. aureus released significantly less soluble CP5 in vitro and in vivo. The release of soluble CP8 by S. aureus may contribute to the inability of CP8 vaccines or antibodies to protect against serotype 8 staphylococcal infections.
authors.affiliation: a Division of Infectious Diseases , Brigham and Women's Hospital and Harvard Medical School , Boston , MA , USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: a Division of Infectious Diseases , Brigham and Women's Hospital and Harvard Medical School , Boston , MA , USA.
authors.forename: Saeyoung
authors.initials: S
authors.lastname: Park
authors.affiliation: a Division of Infectious Diseases , Brigham and Women's Hospital and Harvard Medical School , Boston , MA , USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Thompson
authors.affiliation: a Division of Infectious Diseases , Brigham and Women's Hospital and Harvard Medical School , Boston , MA , USA.|b Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: a Division of Infectious Diseases , Brigham and Women's Hospital and Harvard Medical School , Boston , MA , USA.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D016667:Bacterial Capsules / Q000276:immunology* / Q000378:metabolism; D007116:Immunization, Passive; D066298:In Vitro Techniques; D051379:Mice; D010587:Phagocytosis; D065288:Serogroup; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000737:chemistry / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; C054106:capsular polysaccharide, type 5, Staphylococcus aureus; C064836:capsular polysaccharide, type 8, Staphylococcus aureus
keywords: bacteremia; capsular polysaccharide; monoclonal antibodies; staphylococcus aureus