The invention features a method of vaccinating a mammal against Staphylococcus aureus which includes the steps of: a) identifying a mammal at risk for the development of a Staphylococcus aureus skin or soft tissue infection; and b) administering to said mammal an immunogenic amount of a vaccine that includes a polypeptide including an isolated agglutinin-like sequence (Als) 3 protein (Als3p), or an immunogenic fragment thereof, in a pharmaceutically acceptable medium.