The Vaccine Potential of Heat-killed Attenuated Strain of Salmonella

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　Live attenuated Salmonella strains are thought to be potential vaccines or vaccine vectors for delivery of recombinantly expressed vaccine antigens(Ags). A non-replicative recombinant mutant strain of Salmonella(rSalmonella)that expresses fragment C of tetanus toxin(Tox C)has been shown to be strongly immunogenic, causing induction of significant systemic and mucosal antibody(Ab)responses against the Tox C Ag. However, since previous studies reported that administration of live attenuated strains of Salmonella resulted in side effects, it is preferable to use inactivated bacterial vaccines. Thus, in this study, we assessed the immunogenicity of a heat-killed attenuated strain of rSalmonella. The results showed that oral immunization with heat-killed rSalmonella-Tox C induced tetanus toxoid(TT)-specific systemic IgM Ab responses at levels indistinguishable from those of mice administered live bacteria. However, rSalmonella-Tox C had to be administered at a 10-fold higher oral dose than live bacteria to produce similar levels of TT-specific IgM-forming cells. Even at this higher dose, heat-killed rSalmonella-Tox C induced TT-specific systemic IgG Ab responses that were significantly lower than those obtained in mice dosed with live bacteria. Furthermore, no anti-TT IgA response was detected in the intestinal secretions of mice that were orally dosed with heat-killed rSalmonella-Tox C. Markedly decreased numbers of TT-specific IgG- and IgA-producing cells were detected in the lymph nodes of mice immunized with rSalmonella-Tox C. These results suggest that heat-killed rSalmonella-Tox C may not be appropriate for use as an oral vaccine or vaccine vector.