ORAL IMMUNIZATION WITH RECOMBINANT SALMONELLA-TYPHIMURIUM EXPRESSING SURFACE PROTEIN ANTIGEN-A (SPAA) OF STREPTOCOCCUS-SOBRINUS - EFFECTS OF THE SALMONELLA VIRULENCE PLASMID ON THE INDUCTION OF PROTECTIVE AND SUSTAINED HUMORAL RESPONSES IN RATS

Recombinant strains of Salmonella typhimurium have been studied as ant igen delivery systems to determine their effectiveness as multivalent vaccines. Here we compare the efficacy to two strains of S. typhimuriu m, chi 4072(pYA2905) and chi 3987(pYA2905), expressing SpaA of Strepto coccus sobrinus 6715 as oral vaccines for dental caries. Both strains are attenuated Delta cya Delta crp Delta asd mutants with their Asd(-) phenotypes complemented by the Asd(+) plasmid pYA2905, which also enc odes a peptide fragment of SpaA. S. typhimurium chi 3987(pYA2905), unl ike S. typhimurium chi 4072(pYA2905), contains the 100 kb S. typhimuri um virulence plasmid. Fischer rats were orally immunized with similar to 10(9) S. typhimurium chi 3987(pYA2905) or chi 4072(pYA2905) and the n challenged with cariogenic S. sobrinus 6715. Rats orally immunized w ith either strain of recombinant Salmonella developed salivary IgA ant i-spaA responses and had lower levels of S. sobrinus-induced dental ca ries than nonimmunized, infected animals. In a second series of experi ments, the kinetics and isotype of the serum and salivary antibody res ponses were determined in rats orally immunized with S. typhimurium ch i 3987(pYA2905) or chi 4072(pYA2905) on weeks 0 and 8. IgG and IgM ser um antibody responses to SpaA and S. typhimurium were detected after t he primary and secondary immunizations, and the secondary immunization boosted serum IgG anti-Salmonella activity. In general, animals immun ized with chi 3987(pYA2905) had higher serum anti-SpaA, as well as ser um and salivary anti-Salmonella, responses than animals immunized with chi 4072(pYA2905). This study demonstrates the effective use of two r ecombinant S. typhimurium strains as oral vaccines for inducing protec tive and sustained immune responses against a mucosal pathogen and sug gests that the recombinant Salmonella vaccine strain carrying the viru lence plasmid induced similar or higher protective immune responses th an the strain lacking the virulence plasmid. Copyright (C) 1996.