Staphylococcus aureus is an opportunistic gram positive bacterium that predominantly colonises the anterior nares as part of the normal microflora of 20-30% of the population. With the ability to infect most sites in the body once colonised, S. aureus can cause a variety of diseases – from superficial skin infections to invasive bacteraemia and sepsis. New Zealand has some of the highest rates of S. aureus infection in the developed world and increasing antibiotic resistance is reducing treatment options. Development of a vaccine offers an alternative, long-term approach to the treatment of S. aureus infection. We are investigating the utility of PilVax as a mucosal delivery system of S. aureus antigens to generate immune responses at the site of colonisation. PilVax is a Lactococcus lactis strain engineered to express Streptococcus pyogenes pili on its surface. Each bacterium expresses multiple pili, with each pili comprising 50-100 repeated subunits. An antigenic peptide from S. aureus inserted within each subunit results in an estimated thousand copies of the antigen on the surface of each L. lactis. There are a number of S. aureus linear B cell epitopes identified from cell wall-anchored proteins involved in mucosal colonisation that are ideal candidates for PilVax. We have chosen well characterised, highly conserved S. aureus peptide vaccine candidates from Fibronectin Binding Protein A (FnBP) and Manganese Transport protein C (MntC) as initial targets. Mice will be vaccinated intranasally with Staphy-PilVax strains and assessed for the development of specific local and systemic antibody responses. Vaccinated mice that develop a robust antibody response will be challenged intranasally with a mouse adapted S. aureus strain to determine whether vaccination with Staphy-PilVax can attenuate S. aureus colonization.