title: Staphylococcus aureus capsule type 8 antibodies provide inconsistent efficacy in murine models of staphylococcal infection.
abstract: Staphylococcus aureus is a clinically important capsule-forming bacterium. The capsule polysaccharide (CPs) occurs as different chemical structures depending on the serotype of the organism, but one form, capsular polysaccharide type 8 (CPs8) found in clinical isolates, is largely unstudied. The potential of CPs8 as a vaccine target was evaluated using two approaches. The first approach used a conjugate vaccine, made by chemically linking purified CPs8 to the outer membrane protein complex of N. meningitidis serotype B (OMPC). In efficacy studies, the CPs8-OMPC conjugate vaccine was immunogenic in Balb/c mice, however the immune response gave no protection from death after a lethal intravenous (IV) challenge with S. aureus Becker. In the second approach, two monoclonal antibodies were produced against CPs8 (mAbs 8E8 and 1C10). These were found to have functional activity in an opsonophagocytic killing assay (OPA), and provided protection from a lethal challenge when bacteria were pre-opsonized ex vivo before intra-peritoneal (IP) challenge. However, mAb 8E8 was not efficacious in the lethal challenge model, in which antibodies were passively transferred to the peritoneum and the animals were infected via the tail vein 18-24 h later. Additionally, the monoclonal antibodies did not opsonize capsule-expressing S. aureus Becker obtained from in vivo growth conditions. These results indicated that functional capsule antibodies may not be sufficient for protection from S. aureus under all in vivo conditions.
authors.affiliation: Merck Research Labs, Merck and Co., Inc., West Point, PA 19486, USA.
authors.forename: James
authors.initials: J
authors.lastname: Cook
authors.forename: Robert
authors.initials: R
authors.lastname: Hepler
authors.forename: Greg
authors.initials: G
authors.lastname: Pancari
authors.forename: Nelly
authors.initials: N
authors.lastname: Kuklin
authors.forename: Hongxia
authors.initials: H
authors.lastname: Fan
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Wang
authors.forename: Leslie
authors.initials: L
authors.lastname: Cope
authors.forename: Charles
authors.initials: C
authors.lastname: Tan
authors.forename: Joseph
authors.initials: J
authors.lastname: Joyce
authors.forename: Jan
authors.initials: J
authors.lastname: Onishi
authors.forename: Donna
authors.initials: D
authors.lastname: Montgomery
authors.forename: Annaliesa
authors.initials: A
authors.lastname: Anderson
authors.forename: Tessie
authors.initials: T
authors.lastname: McNeely
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D016667:Bacterial Capsules / Q000276:immunology*; D005260:Female; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D055355:Opsins / Q000276:immunology; D013203:Staphylococcal Infections / Q000517:prevention & control* / Q000628:therapy*; D013209:Staphylococcal Vaccines / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D016019:Survival Analysis; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D055355:Opsins; D013209:Staphylococcal Vaccines; D018074:Vaccines, Conjugate