Enhancing effect of targeted intestinal delivery of Alhagi honey Polysaccharide-Alum Pickering emulsion adjuvant on the immune response to the BVDV vaccine in cattle

Background The mucosa represents the first line of defense against pathogenic invasion, triggering strong mucosal immunity by vaccination for the prevention of infectious diarrheal diseases. Methods In this study, a new assembled Pickering emulsion (AHPPE) was created. This emulsion was constructed by employing an Alum adjuvant (Alum) loaded with Alhagi honey polysaccharide (AHP)-a known enhancer of intestinal mucosal immunity-as the shell, and squalene containing all-trans retinoic acid (RA), an agent targeting intestinal mucosa, as the core, utilizing ultrasonic emulsification techniques. Furthermore, the systemic and mucosal immune responses elicited by AHPPE as an adjuvant for bovine viral diarrhea virus (BVDV) vaccines, along with the associated mechanistic pathways, were investigated. Results The results showed that AHPPE had raspberry-like morphology with a mean particle size of around 2000 nm and a positive surface charge. The emulsion proved to have effective loading capacity for BVDV vaccine antigen and good stability for 30 days. When used as an adjuvant for BVDV vaccine, AHPPE greatly enhanced the titers of BVDV-specific IgG and IgA antibodies and the expression of cytokine interleukin-10 (IL-10), chemokine CCL28, and chemokine receptor CCR9 ( P  < 0.05). Transcriptomic analysis revealed that AHPPE was highly phagocytosed by dendritic cells (DCs), which in turn upregulated the expression of Toll-like receptors and major histocompatibility complex class II (MHC II) molecules, thereby activating T and B lymphocytes to trigger strong systemic immune responses. At the same time, induction of chemokines enabled DCs to migrate specifically to the intestinal tract, triggering intestinal mucosal immune activation. The authenticity of the sequencing data was further validated using confocal microscopy and enzyme-linked immunosorbent assay (ELISA). Conclusion To conclude, the current study provides evidence that AHPPE is a viable vaccine adjuvant for BVDV, which not only generates a robust systemic immune response but also efficiently induces an intestine-targeted mucosal immune response through inducing extensive dendritic cell chemotaxis.