Salmonella Typhi Omp S1 and Omp S2 porins are potent protective immunogens with adjuvant properties.

Salmonella enterica serovar Typhi ( S. Typhi) is the causal agent of typhoid fever, a disease that primarily affects developing countries. Various antigens from this bacterium have been reported to be targets of the immune response. Recently, the S. Typhi genome has been shown to encode two porins - Omp S1 and Omp S2 - which are expressed at low levels under in vitro culture conditions. In this study, we demonstrate that immunizing mice with either Omp S1 or Omp S2 induced production of specific, long-term antibody titres and conferred protection against S. Typhi challenge; in particular, Omp S1 was more immunogenic and conferred greater protective effects than Omp S2. We also found that Omp S1 is a Toll-like receptor 4 ( TLR4) agonist, whereas Omp S2 is a TLR2 and TLR4 agonist. Both porins induced the production of tumour necrosis factor and interleukin-6, and Omp S2 was also able to induce interleukin-10 production. Furthermore, Omp S1 induced the over-expression of MHC II molecules in dendritic cells and Omp S2 induced the over-expression of CD40 molecules in macrophages and dendritic cells. Co-immunization of Omp S1 or Omp S2 with ovalbumin ( OVA) increased anti- OVA antibody titres, the duration and isotype diversity of the OVA-specific antibody response, and the proliferation of T lymphocytes. These porins also had adjuvant effects on the antibody response when co-immunized with either the Vi capsular antigen from S. Typhi or inactivated 2009 pandemic influenza A( H1 N1) virus [ A( H1 N1)pdm09]. Taken together, the data indicate that Omp S1 and Omp S2, despite being expressed at low levels under in vitro culture conditions, are potent protective immunogens with intrinsic adjuvant properties. [ABSTRACT FROM AUTHOR]