A recombinant clumping factor A-containing vaccine induces functional antibodies to Staphylococcus aureus that are not observed after natural exposure.
Staphylococcus aureus is a Gram-positive pathogen that causes devastating disease and whose pathogenesis is dependent on interactions with host cell factors. Staphylococcal clumping factor A (ClfA) is a highly conserved fibrinogen (Fg)-binding protein and virulence factor that contributes to host tissue adhesion and initiation of infection. ClfA is being investigated as a possible component of a staphylococcal vaccine. We report the development of an Fg-binding assay that is specific for ClfA-mediated binding. Using the assay, we show that despite the presence of anti-ClfA antibodies, human sera from unvaccinated subjects are unable to prevent the binding of S. aureus to an Fg-coated surface. In contrast, antibodies elicited by a recombinant ClfA-containing vaccine were capable of blocking the ClfA-dependent binding of a diverse and clinically relevant collection of staphylococcal strains to Fg. These functional antibodies were also able to displace S. aureus already bound to Fg, suggesting that the ligand-binding activity of ClfA can be effectively neutralized through vaccination.
Pfizer Vaccine Research, Pearl River, New York, USA.
Julio
J
Hawkins
Srinivas
S
Kodali
Yury V
YV
Matsuka
Lisa K
LK
McNeil
Terri
T
Mininni
Ingrid L
IL
Scully
John H
JH
Vernachio
Elena
E
Severina
Douglas
D
Girgenti
Kathrin U
KU
Jansen
Annaliesa S
AS
Anderson
Robert G K
RG
Donald
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001422:Bacterial Adhesion; D003030:Coagulase / Q000276:immunology* / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control; D013209:Staphylococcal Vaccines / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000472:pathogenicity
D000907:Antibodies, Bacterial; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D013209:Staphylococcal Vaccines; D005340:Fibrinogen