IMMUNIZATION OF MICE BY ORAL COLONIZATION WITH LIVE RECOMBINANT COMMENSAL STREPTOCOCCI

To test the use of recombinant streptococci as live vaccine vectors, c olonizationl immunization experiments were performed with Streptococcu s gordonii expressing heterologous cell-surface antigens. Three isogen ic strains of S. gordonii were used. a wild-type, a recombinant expres sing the M6 protein of Streptococcus pyogenes, and a recombinant expre ssing the E7 protein of human papillomavirus type 16 as a fusion with the M6 protein. A single dose of live bacteria was used to inoculate o utbred mice, and it was found that. (i) mice were stably colonized by a single intrasalloral inocuhum of S. gordonii; (ii) recombinant strai ns were equally effective as wild-type in colonizing mice, (iii) two m onths after the inoculum, oral/pharyngeal swabs of 83.3% of animals we re still positive for isolation of S. gordonii, (iv) recombinant S. go rdonii isolated from colonized mice were always positive for expressio n of the heterologous antigens, (v) live bacteria induced a systemic i mmune response, since sera of mice colonized with recombinant S. gordo nii contained IgG specific for the heterologous cell-surface antigens, (vi) this immune response depended upon the effective colonization by live bacteria, since killed bacteria did not induce such a response.