Recombinant Bacillus subtilis Spores Elicit Th1/Th17-Polarized Immune Response in a Murine Model of Helicobacter pylori Vaccination

Abstract

Current progress in research on vaccines against Helicobacter pylori emphasizes the significance of eliciting the Th1/Th17-polarized immune response. Such polarization can be achieved by selection of appropriate antigen and adjuvant. In this study, we wanted to check the polarization of the immune response elicited by UreB protein of Helicobacter acinonychis delivered by recombinant Bacillus subtilis spores upon oral immunization. B. subtilis spores presenting fragment of UreB protein and able to express entire UreB in vegetative cells after germination were orally administered to mice along with aluminum hydroxide or recombinant spores presenting IL-2 as an adjuvant. The pattern of cytokines secreted by sensitized splenocytes assessed by the cytometric bead array clearly indicated polarization of the immune response toward both Th1 and Th17 in mice immunized with the use of above-mentioned adjuvants. Obtained result is promising regarding the usage of recombinant spores in formulations of vaccines against H. pylori and line up with the current state of research emphasizing the key role of appropriate adjuvants.

The combination of recombinant and non-recombinant Bacillus subtilis spore display technology for presentation of antigen and adjuvant on single spore

“…FliD-presenting spores of the wild type strain led to bias of the response towards Th1 and Th17. Such polarization has also been observed in our previous studies involving use of recombinant spores presenting FliD fragment [ 27 , 28 ]. Lack of IL-6 (data not shown), a cytokine characteristic for Th17 polarization of the immune response, seems to result from technical problems in detecting this cytokine with the method used in our study.…”

The choice of anchoring protein influences interaction of recombinant Bacillus spores with the immune system

“…To check how the choice of anchoring protein influences interaction of the recombinant spores with the immune system, we performed mucosal immunization of mice with all variants of the FliD-presenting spores. Since results of our previous research indicated that the recombinant spores did not elicit immune response in mice upon oral immunization without the use of appropriate adjuvants (Hinc et al, 2014;Stasiłojć et al, 2015), we decided to administrate spores by the intranasal route, which was shown to be compatible with such antigen delivery systems (Huang et al, 2010;. We were not able to detect a statistically significant increase in levels of FliD-specific antibodies in sera, lungs or gastrointestinal tracts of immunized animals (data not shown).…”

Other Helicobacters and gastric microbiota

“…Oral administration of Bacillus subtilis spores expressing the UreB protein of H. acinonychis resulted in a Th1 and Th17 polarization. 16 This specific cellular immune response has been associated with protection against H. pylori infections. 17,18 Administration of a H. pylori urease-based subunit vaccine resulted in a reduction of H. felis colonization in mice.…”