A probiotic treatment increases the immune response induced by the nasal delivery of spore-adsorbed TTFC

Abstract

Background: Spore-forming bacteria of the Bacillus genus are widely used probiotics known to exert their beneficial effects also through the stimulation of the host immune response. The oral delivery of B. toyonensis spores has been shown to improve the immune response to a parenterally administered viral antigen in mice, suggesting that probiotics may increase the efficiency of systemic vaccines. We used the C fragment of the tetanus toxin (TTFC) as a model antigen to evaluate whether a treatment with B. toyonensis spores affected the immune response to a mucosal antigen. Results: Purified TTFC was given to mice by the nasal route either as a free protein or adsorbed to B. subtilis spores, a mucosal vaccine delivery system proved effective with several antigens, including TTFC. Spore adsorption was extremely efficient and TTFC was shown to be exposed on the spore surface. Spore-adsorbed TTFC was more efficient than the free antigen in inducing an immune response and the probiotic treatment improved the response, increasing the production of TTFC-specific secretory immunoglobin A (sIgA) and causing a faster production of serum IgG. The analysis of the induced cytokines indicated that also the cellular immune response was increased by the probiotic treatment. A 16S RNA-based analysis of the gut microbial composition did not show dramatic differences due to the probiotic treatment. However, the abundance of members of the Ruminiclostridium 6 genus was found to correlate with the increased immune response of animals immunized with the spore-adsorbed antigen and treated with the probiotic. Conclusion: Our results indicate that B. toyonensis spores significantly contribute to the humoral and cellular responses elicited by a mucosal immunization with spore-adsorbed TTFC, pointing to the probiotic treatment as an alternative to the use of adjuvants for mucosal vaccinations.

Secreted Chemicals From Probiotic Bacteria Potentiate Th1 Pattern of Immune Cells and Apoptosis Induction in Breast Cancer and Gastric Adenocarcinoma Cell Lines

“…Also, Santos et al reported the same results in which B. toyonensis probiotic bacterium increased IFN-γ cytokine in the vaccine system [32]. Our results are in line with the results of other studies.…”

Inhibitory Effect of a Microecological Preparation on Azoxymethane/Dextran Sodium Sulfate-Induced Inflammatory Colorectal Cancer in Mice

“…Actually, Alloprevotella has been regarded as the cancer-related bacteria in colon cancer or visceral leishmaniasis (30,31). Moreover, a previous study showed that the abundance of the Ruminiclostridium genus was related to the enhancement of animal immune responses to spore adsorbent antigen and probiotics (32). Similarly, Prevotellaceae_UCG_001 was overrepresented in AOM/DSS mice in comparison to controls (33).…”

Nasal Immunization with the C-Terminal Domain of Bcla3 Induced Specific IgG Production and Attenuated Disease Symptoms in Mice Infected with Clostridioides difficile Spores

“…In this context, it is known that recombinant spores of B. subtilis administered by gavage germinate in the stomach and small intestine and due to low oxygen present in the large bowel environment they re-sporulate displaying the heterologous antigen again [ 48 , 49 , 50 ] therefore, the oral delivery of recombinant B. subtilis spores would be also considered and interesting option since it allows higher doses and number of immunizations. Additionally, the use of adjuvants with immunostimulatory capacities, such as Toll-Like Receptors (TLR) and NOD-Like Receptor (NLR) ligands [ 51 ] or probiotics [ 52 ] might boost the expected immune response. A recent study has shown that humoral and cellular immune responses observed in mice nasally immunized with B. subtilis spores displaying the C fragment of the tetanus toxin (TTFC) on the surface were enhanced in mice previously submitted to Bacillus toyonencis as probiotic [ 52 ].…”

“…Additionally, the use of adjuvants with immunostimulatory capacities, such as Toll-Like Receptors (TLR) and NOD-Like Receptor (NLR) ligands [ 51 ] or probiotics [ 52 ] might boost the expected immune response. A recent study has shown that humoral and cellular immune responses observed in mice nasally immunized with B. subtilis spores displaying the C fragment of the tetanus toxin (TTFC) on the surface were enhanced in mice previously submitted to Bacillus toyonencis as probiotic [ 52 ]. Therefore, the use of these kinds of strategies would contribute to an improvement in this work.…”