A Recombinant Clumping Factor A-Containing Vaccine Induces Functional Antibodies to Staphylococcus aureus That Are Not Observed after Natural Exposure
- 1 October 2012
- journal article
- research article
- Published by American Society for Microbiology in Clinical and Vaccine Immunology
- Vol. 19 (10), 1641-1650
- https://doi.org/10.1128/cvi.00354-12
Abstract
Staphylococcus 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 ofS. 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 displaceS. aureusalready bound to Fg, suggesting that the ligand-binding activity of ClfA can be effectively neutralized through vaccination.Keywords
This publication has 36 references indexed in Scilit:
- Staphylococcus aureus Manganese Transport Protein C Is a Highly Conserved Cell Surface Protein That Elicits Protective Immunity Against S. aureus and Staphylococcus epidermidisThe Journal of Infectious Diseases, 2012
- Fibrinogen Is a Ligand for the Staphylococcus aureus Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMM) Bone Sialoprotein-binding Protein (Bbp)Published by Elsevier BV ,2011
- Identifying protective antigens ofStaphylococcus aureus, a pathogen that suppresses host immune responsesThe FASEB Journal, 2011
- Structural and Biochemical Characterization of Staphylococcus aureus Clumping Factor B/Ligand InteractionsJournal of Biological Chemistry, 2011
- Antibody responses in furunculosis patients vaccinated with autologous formalin-killed Staphylococcus aureusEuropean Journal of Clinical Microbiology & Infectious Diseases, 2011
- Clumping Factor A Interaction with Complement Factor I Increases C3b Cleavage on the Bacterial Surface ofStaphylococcus aureusand Decreases Complement-Mediated PhagocytosisInfection and Immunity, 2010
- Molecular Characterization of the Interaction of Staphylococcal Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMM) ClfA and Fbl with FibrinogenPublished by Elsevier BV ,2010
- Genetic requirements forStaphylococcus aureusabscess formation and persistence in host tissuesThe FASEB Journal, 2009
- Fibrinogen Binding Sites P336 and Y338 of Clumping Factor A Are Crucial for Staphylococcus aureus VirulencePLOS ONE, 2008
- Phase II, Randomized, Double-Blind, Multicenter Study Comparing the Safety and Pharmacokinetics of Tefibazumab to Placebo for Treatment of Staphylococcus aureus BacteremiaAntimicrobial Agents and Chemotherapy, 2006