Discovery of a novel adjuvant for oral vaccine formulations

CASTRO, CELESTE PUEBLAS; CORIA, LORENA; LAURA BRUNO; SAPOSNIK, LUCAS; PHILIPPE HERMAND; STÉPHANE TEMMERMAN; KARINA PASQUEVICH; CASSATARO JULIANA

Ciudad del Cabo, Sudáfrica

Congreso; 18th International Congress of Immunology - International Union of Immunological Societies (IUIS); 2023

In our laboratory, we have shown that the protease inhibitor U-Omp19 from Brucella spp. is an oral vaccine adjuvant that protects co-delivered antigens (Ags) from proteolysis in the gastrointestinal tract and increases Ag-specific adaptive immune responses. To our knowledge there are no other reports describing the use of protease inhibitors from bacteria as vaccine adjuvants. Thus, to discover new oral adjuvants we performed an in-silico and in vivo screening of bacterial protease inhibitors. From this screening, we selected Ecotin from Salmonella spp. as an oral adjuvant candidate.The goal of this work is to evaluate if Ecotin could be used as an adjuvant for oral vaccines. For this aim, mice were immunized orally with two viral Ags simultaneously with or without Ecotin. The levels of Ag-specific IgA and IgG in feces and/or serum were determined by ELISA and Ag-specific B and T cell responses were also evaluated by flow cytometry and ELISPOT.Ecotin-adjuvanted formulations induced a sustainable Ag-specific IgA response in feces compared to the administration of Ags alone. Ecotin-adjuvanted formulations also induced higher levels of Ag-specific IgG and IgA in serum compared to the Ags alone group. Furthermore, Ecotin-adjuvanted formulations induced higher levels of Ag-specific IgA+ B cells and plasmablasts at Peyer’s patches, Ag-specific IgG+ cells in the bone marrow and Ag-specific CD19+ B220+ IgD- CD38+ in the spleen. Evaluation of T cell responses showed a higher percentage of T follicular helper cells in Peyer’s patches and Ag-specific CD4+IFN-γ+, CD4+IL-17+ and CD8+IL-2+ T cells in mesenteric lymph nodes when the Ags were co-administered with Ecotin, compared to Ags alone group. Altogether, these results show that Ecotin could be used as adjuvant for oral viral vaccines, since it is able to induce a specific sustainable adaptive immune response when co-administrated with two different Ags.