title: Heterogeneous in vivo expression of clumping factor A and capsular polysaccharide by Staphylococcus aureus: implications for vaccine design.
abstract: There is a clear unmet medical need for a vaccine that would prevent infections from Staphylococcus aureus (S. aureus). To validate antigens as potential vaccine targets it has to be demonstrated that the antigens are expressed in vivo. Using murine bacteremia and wound infection models, we demonstrate that the expression of clumping factor A (ClfA) and capsular polysaccharide antigens are heterogeneous and dependent on the challenge strains examined and the in vivo microenvironment. We also demonstrate opsonophagocitic activity mediated by either antigen is not impeded by the presence of the other antigen. The data presented in this report support a multiantigen approach for the development of a prophylactic S. aureus vaccine to ensure broad coverage against this versatile pathogen.
authors.affiliation: Wyeth Vaccine Research, 401 N. Middletown Road, Pearl River, NY 10965, USA.
authors.forename: Jasdeep S
authors.initials: JS
authors.lastname: Nanra
authors.forename: Yekaterina
authors.initials: Y
authors.lastname: Timofeyeva
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Buitrago
authors.forename: Bret R
authors.initials: BR
authors.lastname: Sellman
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Dilts
authors.forename: Pamela
authors.initials: P
authors.lastname: Fink
authors.forename: Lorna
authors.initials: L
authors.lastname: Nunez
authors.forename: Michael
authors.initials: M
authors.lastname: Hagen
authors.forename: Yury V
authors.initials: YV
authors.lastname: Matsuka
authors.forename: Terri
authors.initials: T
authors.lastname: Mininni
authors.forename: Duzhang
authors.initials: D
authors.lastname: Zhu
authors.forename: Viliam
authors.initials: V
authors.lastname: Pavliak
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Green
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.forename: Annaliesa S
authors.initials: AS
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis*; D016470:Bacteremia / Q000276:immunology; D016667:Bacterial Capsules / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D003030:Coagulase / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D015195:Drug Design; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D013209:Staphylococcal Vaccines / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D013209:Staphylococcal Vaccines