Heterogeneous in vivo expression of clumping factor A and capsular polysaccharide by Staphylococcus aureus: implications for vaccine design.
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.
Nanra
Jasdeep S
JS
Wyeth Vaccine Research, 401 N. Middletown Road, Pearl River, NY 10965, USA.
Timofeyeva
Yekaterina
Y
Buitrago
Sandra M
SM
Sellman
Bret R
BR
Dilts
Deborah A
DA
Fink
Pamela
P
Nunez
Lorna
L
Hagen
Michael
M
Matsuka
Yury V
YV
Mininni
Terri
T
Zhu
Duzhang
D
Pavliak
Viliam
V
Green
Bruce A
BA
Jansen
Kathrin U
KU
Anderson
Annaliesa S
AS
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*
D000942:Antigens, Bacterial; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D013209:Staphylococcal Vaccines