A Recombinant Clumping Factor A-Containing Vaccine Induces Functional Antibodies to Staphylococcus aureusThat Are Not Observed after Natural Exposure

Autor: Hawkins, Julio, Kodali, Srinivas, Matsuka, Yury V., McNeil, Lisa K., Mininni, Terri, Scully, Ingrid L., Vernachio, John H., Severina, Elena, Girgenti, Douglas, Jansen, Kathrin U., Anderson, Annaliesa S., Donald, Robert G. K.
Zdroj: Clinical and Vaccine Immunology (formerly CDLI); August 2012, Vol. 19 Issue: 10 p1641-1650, 10p
Abstrakt: ABSTRACTStaphylococcus aureusis 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. aureusto 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. aureusalready bound to Fg, suggesting that the ligand-binding activity of ClfA can be effectively neutralized through vaccination.
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