Staphylococcus aureus is a major cause of both nosocomial and community-acquired infections. Antibiotics have been the treatment of choice in the past; however there has been a dramatic increase in the number of antibiotic resistant S. aureus isolates. Thus, alternative prevention and treatment strategies are desperately needed. Microbial adhesion is the first step in the pathogenic process of bacterial infections and therefore is an attractive target for novel immunotherapeutics. S. aureus colonizes the host by attaching to host tissues or serum conditioned implanted biomaterials through a family of adhesins called MSCRAMM that recognize and specifically bind to distinct components in the host's extracellular matrix. Preliminary results generated by Inhibitex, Inc., has demonstrated that MSCRAMM specific high affinity blocking antibodies can be generated and that these antibodies protect animals against infection. The goal of this proposal is to design and produce a prototype MSCRAMM-based multi-component vaccine, characterize the immune response of animals immunized with the vaccine, and test the ability of the vaccine to protect animals against S. aureus infections.
The need for novel approaches to fight S. aureus infections are necessary, especially in the light of the increased emergence of antibiotic resistant organisms. MSCRAMMs provide an excellent target for intervention since they participate in the first step in the development of most infections. The prophylactic extensions of this technology are extremely appealing given the escalating cost of health care.