Protection against experimental Staphylococcus aureus arthritis by vaccination with clumping factor A, a novel virulence determinant

The importance of the fibrinogen-binding adhesin clumping factor A (ClfA) i n the pathogenesis of Staphylococcus aureus septic arthritis was examined i n an animal model. The protective effect of active and passive immunization with ClfA also was investigated in S. aureus infection models. The severit y of arthritis was markedly reduced in mice challenged intravenously with a clfA mutant, compared with mice infected with the wild-type strain. Mice i mmunized with recombinant ClfA and challenged with S. aureus developed less -severe arthritis than did mice immunized with a control antigen. Passive i mmunization of mice with rat and rabbit anti-ClfA antibodies protected agai nst S. aureus arthritis and sepsis-induced death, indicating that the prote ction by active immunization is antibody mediated. Taken together, these da ta strongly suggest that ClfA is a crucial virulence determinant for septic arthritis and an excellent target for the generation of immune therapies d irected against S. aureus.