MUCOSAL AND SYSTEMIC IMMUNE-RESPONSES TO A RECOMBINANT PROTEIN EXPRESSED ON THE SURFACE OF THE ORAL COMMENSAL BACTERIUM STREPTOCOCCUS-GORDONII AFTER ORAL COLONIZATION

To circumvent the need to engineer pathogenic microorganisms as live v accine-delivery vehicles, a system was developed which allowed for the stable expression of a wide range of protein antigens on the surface of Grampositive commensal bacteria. The human oral commensal Streptoco ccus gordonii was engineered to surface express a 204-amino acid aller gen from hornet venom (Ag5.2) as a fusion with the anchor region of th e M6 protein of Streptococcus pyogenes. The immunogenicity of the h16- Ag5.2 fusion protein was assessed in mice inoculated orally and intran asally with a single dose of recombinant bacteria, resulting in the co lonization of the oral/pharyngeal mucosa for 10-11 weeks. A significan t increase of Ag5.2-specific IgA with relation to the total IgA was de tected in saliva and lung lavages when compared with mice colonized wi th wild-type S. gordonii. A systemic IgG response to Ag5.2 was also in duced after oral colonization. Thus, recombinant Gram-positive commens al bacteria may be a safe and effective way of inducing a local and sy stemic immune response.