Nanoemulsion adjuvant augments retinaldehyde dehydrogenase activity in dendritic cells and regulates expression of gut homing receptors on T cells

Abstract

Abstract Mucosal surfaces are the primary point of entry for most infectious agents. Therefore, induction of mucosal immune responses serves as the primary defense by preventing and clearing pathogens. In order to mount an effective immune response, secretory IgA and T cell homing towards mucosal surfaces are two very important factors. Conventional vaccines induce strong systemic immunity, but often fail to produce mucosal immune responses. Our group has developed an oil-in-water nanoemulsion which has been shown to provide protection against mucosal pathogens when administered as an intranasal vaccine adjuvant. In the present study, we demonstrate that intranasal immunization with nanoemulsion indirectly activates the retinaldehyde dehydrogenase in dendritic cells, leading to an increase in secretory IgA production as well as expression of α4β7 and CCR9 gut homing receptors on the mesenteric lymph node cells. Ex vivo stimulation of splenocytes from NE immunized animals established increase in Th1/Th17 cytokines while suppressing Th2, suggesting RALDH increase does not suppress Th1/Th17 response. Our nanoemulsion based adjuvant activates retinaldehyde dehydrogenase without possessing any active ligand and imprints T cells for gut homing without altering systemic immunity. These results provide new insights into the mechanism of our nanoemulsion adjuvant and have significant implications for the design of effective mucosal vaccines.