Most pathogens gain access to their host through mucosal surfaces. It is therefore desirable to develop mucosal vaccines that elicit an immune response to prevent this crucial first step in infection. Current mucosal vaccines are live attenuated strains of pathogens. More recent efforts have focused on the use of recombinant non-pathogenic gram-positive bacteria as live vaccine delivery vectors. Here I have tested the potential of Lactococcus lactis to be used as a vaccine vector. A recombinant strain of L. lactis has been constructed which expresses and displays on its surface the C repeat region (CRR) of the M6 protein of Streptococcus pyogenes. I show that nasal vaccination of mice with this strain elicited strong salivary IgA and serum lgG response. These responses protected mice against a nasal challenge with S. pyogenes. Subcutaneous vaccination with the same strain of L. lactis produced a strong serum lgG response, but no salivary lgA response. Subcutaneous vaccination did not protect the mice against nasal infections when the mice were challenged with S. pyogenes. The immune response and protection afforded by concomitant vaccination by both nasal and subcutaneous routes were better that that seen in nasal vaccination alone. This study shows that an effective vaccine against S. pyogenes is possible using L. lactis as a vaccine vector. It also opens up the potential of L. lactis to be used in the development of vaccines to other mucosal infections. / Graduation date: 2004