A novel murine experimental wound infection model was used to assess the efficacy of multi-component immunization against Staphylococcus aureus infection. Necrotic lesions were induced in mice with venom from Bothrops asper and infected with a low inoculum， 1 × 10 CFU. The wound infection model therefore more resembles a clinical case of S. aureus infection compared with conventional infection models where far more bacteria are required. Before infection， mice were immunized with four recombinant S.aureus proteins expressed from Escherichia coli: (i) domains 1-3 of Extracellular adherence protein (Eap)， (ii) Efb - D (fusion protein combining Extracellular fibrinogen binding protein (Efb) and a fibronectin binding domain (D) of the fibronectin binding protein (FnBP) and (iii) clumping factor A (ClfA). In the immunized group， lower bacterial colonization， undisturbed crust formation and significantly faster wound healing were found compared with the unimmunized control group. Efb and Eap have previously been found to impair wound healing and neutralization of these proteins by antibodies restores a more natural wound healing process. This effect is further also enhanced by the proposed opsonic activity of antibodies against ClfA and FnBP.