Salmonella Typhi OmpS1 and OmpS2 porins are potent protective immunogens with adjuvant properties

Abstract

Summary 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 – which are expressed at low levels under in vitro culture conditions. In this study, we demonstrate that immunizing 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 4 (TLR4) agonist, whereas OmpS2 is a TLR2 and TLR4 agonist. Both porins induced the production of tumour necrosis factor and interleukin‐6, and OmpS2 was also able to induce interleukin‐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‐immunization 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‐immunized 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.

Immuno-Modulatory Role of Porins: Host Immune Responses, Signaling Mechanisms and Vaccine Potential

“…Porins from many gram-negative bacteria such as Fusobacterium nucleatum , Haemophilus infl uenza e, Helicobater pylori , Neisseria , Salmonella and Shigella spp. induce pro-infl ammatory cytokines like TNFα, IL-6 and IL-1β secretion in a variety of cell lines and primary cells, such as monocytes and macrophages of human and mouse origin (Table 6.1 ) (Tufano et al 1994(Tufano et al , 1995Toussi et al 2012 ;Galdiero et al 2001aGaldiero et al , b , 2004Vitiello et al 2004Vitiello et al , 2011Liu et al 2010 ;Singleton et al 2005 ;Massari et al 2006 ;Al-Bader et al 2004 ;Moreno-Eutimio et al 2013, Galdiero et al 2005, 2006aRay et al 2003 ;Biswas et al 2007 ;Elena et al 2009 ;Pore et al 2012 ). Vibrio cholerae OmpU stimulates monocytes and macrophages to produce TNFα and IL-6 (Sakharwade et al 2013 ).…”

“…Administration of various Salmonella Typhi porins offer protection against infection in mice. OmpA, OmpC, OmpF, OmpS1 and OmpS2 have been studied in this regard (Toobak et al 2013 ;Moreno-Eutimio et al 2013 ;Isibasi et al 1988Isibasi et al , 1992Singh et al 1999 ). OmpS1 and OmpS2 also show adjuvant properties (MorenoEutimio et al 2013 ).…”

IFN-γ–Producing CD4+ T Cells Promote Generation of Protective Germinal Center–Derived IgM+ B Cell Memory against Salmonella Typhi

“…S. Typhi OmpC and OmpF can be purified and produced at large scale for application in humans (17). Such highly purified S. Typhi porins induce longlasting bactericidal Ab responses in mice (18) and exhibit intrinsic adjuvant activity (14,19). Intriguingly, S. Typhi porins have been applied to humans showing that this subunit vaccine is safe and immunogenic and that the B cell response in humans generates IgG and IgM Abs (17), suggesting that both isotypes could contribute to protection against this intracellular pathogen.…”

Immunoproteomic Analysis of Antibody in Lymphocyte Supernatant in Patients with Typhoid Fever in Bangladesh

“…In a mouse model, OmpS2 was also found to be a potent inducer of the innate immune response acting as both a Toll-like receptor 2 (TLR2) and TLR4 agonist (39). In addition, OmpS2 has adjuvant capability, boosting antibody responses when coimmunized with other antigens (39).…”