Unlipidated Outer Membrane Protein Omp16 (U-Omp16) from Brucella spp. as Nasal Adjuvant Induces a Th1 Immune Response and Modulates the Th2 Allergic Response to Cow’s Milk Proteins

Abstract

The discovery of novel mucosal adjuvants will help to develop new formulations to control infectious and allergic diseases. In this work we demonstrate that U-Omp16 from Brucella spp. delivered by the nasal route (i.n.) induced an inflammatory immune response in bronchoalveolar lavage (BAL) and lung tissues. Nasal co-administration of U-Omp16 with the model antigen (Ag) ovalbumin (OVA) increased the amount of Ag in lung tissues and induced OVA-specific systemic IgG and T helper (Th) 1 immune responses. The usefulness of U-Omp16 was also assessed in a mouse model of food allergy. U-Omp16 i.n. administration during sensitization ameliorated the hypersensitivity responses of sensitized mice upon oral exposure to Cow’s Milk Protein (CMP), decreased clinical signs, reduced anti-CMP IgE serum antibodies and modulated the Th2 response in favor of Th1 immunity. Thus, U-Omp16 could be used as a broad Th1 mucosal adjuvant for different Ag formulations.

Oral delivery ofBrucellaspp. recombinant protein U-Omp16 abrogates the IgE-mediated milk allergy

“…It has been previously demonstrated that this newly described PAMP activates dendritic cells through binding to TLR4. 11 These results, in accordance with our previous works, 11,12 prompt us to propose the use U-Omp16 as a mucosal adjuvant to enhance or control an Ag-specific immune response. Of note, the immunomodulatory properties of U-Omp16 were comparable to CpG administration.…”

“…33,12 Briefly, recombinant U-Omp16 was isolated from bacterial cytoplasm and then purified by affinity chromatography with a Ni-NTA resin (Qiagen). Expression and purification of the recombinant protein was checked by SDS-PAGE followed by Coomasie Blue staining and to confirm the identity of the U-Omp16, western blot was performed and developed with anti-Omp16-specific mAb (data not shown).…”

The future of biologics: Applications for food allergy

“…Treatment of mice with peanut allergen bound to chitosan, or cow's milk protein bound to OMP-16, reduced allergen-specific IgE antibody responses and promoted Th1 responses. 107, 108 These studies further suggest that promoting Th1 polarization may be an effective adjunctive therapy for the treatment of food allergy.…”

Allergen-Specific Immunotherapy for Food Allergy: Latest Advances in Vaccines

“…Great efforts are being made to develop novel strategies in animal models exploring combination of mucosal routes [54], bioadhesive carrier systems [34,55], novel immunomodulatory and/or tolerogenic adjuvants [9,10,55,56], immunological drugs to expand Tregs [12] and nanoparticles [56] to prevent or revert food allergy. These finding will undoubtedly provide new parameters to analyze the induction of novel regulatory cell subsets, and cellular and molecular biomarkers for regulatory cell activation, with a direct impact in the design of safer and more effective treatments.…”

“…Understanding this complex geneenvironment interaction will allow us to develop novel generation of treatments that could modify aberrant immune activation and chronic diseases. Based on theses premises the use of Th1 proinflammatory [9,10] or immunosuppressant components [11,12] may compensate the deprived immune stimulation and promotion of counter-regulatory circuits that control the Th2-mediated immunity that governs allergic diseases. However, it is currently suspected that not only can microorganism exposure influence the development of the complex immunoregulatory circuits at mucosal sites, but diet and microbiota-derived metabolites are also implicated.…”