Bereiche

PubMed

DOI

Kontakt

---

Zitation

Art

Zeitschrift

Veröffentlichungsdatum

eISSN (Online)

Kurzbeschreibung/Zielsetzung

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 - OmpS1 and OmpS2 - that are expressed at low levels under in vitro culture conditions. In this study, we demonstrate that immunising mice with either OmpS1 or OmpS2 induced production of specific, long-term antibody titres and conferred protection against S. Typhi challenge; in particular, OmpS1 was more immunogenic and conferred greater protective effects than OmpS2. We also found that OmpS1 is a Toll-like receptor (TLR) 4 agonist, whereas OmpS2 is a TLR2 and TLR4 agonist. Both porins induced the production of TNF and IL-6, and OmpS2 was also able to induce IL-10 production. Furthermore, OmpS1 induced the over-expression of MHC II molecules in dendritic cells and OmpS2 induced the over-expression of CD40 molecules in macrophages and dendritic cells. Co-immunisation of OmpS1 or OmpS2 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-immunised with either the Vi capsular antigen from S. Typhi or inactivated 2009 pandemic influenza A(H1N1) virus (A(H1N1)pdm09). Taken together, the data indicate that OmpS1 and OmpS2, despite being expressed at low levels under in vitro culture conditions, are potent protective immunogens with intrinsic adjuvant properties.