ORAL IMMUNIZATION WITH RECOMBINANT SALMONELLA-TYPHIMURIUM EXPRESSING SURFACE PROTEIN ANTIGEN-A OF STREPTOCOCCUS-SOBRINUS - DOSE-RESPONSE AND INDUCTION OF PROTECTIVE HUMORAL RESPONSES IN RATS

An attenuated, recombinant Salmonella typhimurium mutant, (chi)4072(pY A2905), expressing the surface protein antigen A (SpaA) of Streptococc us sobrinus was investigated for its effectiveness in inducing protect ive immune responses against S. sobrinus-induced dental caries in an e xperimental caries model. Fischer rats were orally immunized with eith er 10(8) or 10(9) CFU of S. typhimurium (chi)4072(pYA2905). Persistenc e of salmonellae in Peyer's patches and spleens and the induction of i mmune responses were determined. Maximum numbers of salmonellae were r ecovered from Peyer's patches of rats within the first week of immuniz ation, with higher numbers recovered from rats given 10(9) CFU than fr om those given 10(8) CFU. Serum anti-Salmonella and anti-SpaA response s increased more rapidly in rats given 10(9) CFU than in rats given 10 (8) CFU. The salivary antibody response to SpaA increased with time, b ut the response varied in the two groups, In a separate study, rats we re orally immunized with the recombinant Salmonella mutant and then ch allenged with cariogenic S. sobrinus 6715. The levels of serum and sal ivary antibody and caries activity were assessed at the termination of the experiment. Higher levels of salivary immunoglobulin A antibody t o SpaA and Salmonella carrier were detected in rats given 10(9) CFU th an in those given 10(8) CFU, and these responses were higher than thos e in nonimmunized controls. Mandibular molars from immunized rats had lower numbers of recoverable streptococci and less extensive carious l esions than those from nonimmunized, control rats. These data indicate that oral immunization with an attenuated recombinant S. typhimurium expressing SpaA of S. sobrinus induces the production of antigen-speci fic mucosal antibody and confers protection against dental caries.