Use of a MAIT-Activating Ligand, 5-OP-RU, as a Mucosal Adjuvant in a Murine Model of Vibrio cholerae O1 Vaccination

Abstract

Background Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in the mucosa with capacity for B cell help. We hypothesize that targeting MAIT cells, using a MAIT activating ligand as an adjuvant, could improve mucosal vaccine responses to bacterial pathogens. Methods We utilized murine models of Vibrio cholerae vaccination to test the adjuvant potential of the MAIT activating ligand, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU). We measured V. cholerae-specific antibody and antibody-secreting cell responses, and used flow cytometry to examine MAIT cell and B cell phenotype, in blood, bronchoalveolar lavage fluid (BALF), and mucosal tissues, following intranasal vaccination with live V. cholerae O1 or a V. cholerae O1 polysaccharide conjugate vaccine. Results We report significant expansion of MAIT cells in the lungs of 5-OP-RU treated mice, and increases in BALF V. cholerae O-specific-polysaccharide IgG responses in our conjugate vaccine model adjuvanted with low-dose 5-OP-RU. No significant differences in humoral responses were found in our live V. cholerae vaccination model. Conclusions Using a murine model, we demonstrate the potential, as well as the limitations, of targeting MAIT cells to improve antibody responses to a mucosal cholera vaccine. Our study highlights the need for future research optimizing MAIT cell targeting for improving mucosal vaccines. One Sentence Summary Targeting mucosal-associated invariant T (MAIT) cells with a mucosal adjuvant in an intranasal cholera vaccine model resulted in significant expansion of lung MAIT cells, but limited improvements in cholera-specific antibody responses.