Mouse anti-Mouse OVA peptide (257-264) bound to H-2Kb complex monoclonal antibody, clone 25-D1.16 [PE/Cy7®]

Cancer therapeutic nanovaccines are ideal tools to inhibit tumor growth and provide the body with continuous protecting immune surveillance. However, the conventional subcutaneous (SC) vaccination normally induces limited anti-tumor immune responses with low therapeutic efficacy. Herein, we devised clay-based nanovaccines and directly delivered them to the spleen via intravenous (IV) injection to induce the stronger anti-tumor immunity with higher efficacy for tumor prevention and treatment. The clay, i.e., layered double hydroxide (LDH) was prepared as nanoadjuvant with the average size from 77 to 285 nm and co-loaded with the model antigen ovalbumin (OVA) and bioadjuvant CpG to form CpG/OVA-LDH (CO-LDH) nanovaccines. We found that CO-LDH-215 (the size of LDH was 215 nm) promoted dendritic cells to present the most antigen, and moreover showed the highest spleen enrichment (similar to 1.67% of CO-LDH-215 enriched in the spleen at 24 h post IV injection). The in vivo immunologic data showed that CO-LDH-215 induced the most potent anti-tumor immune responses and completely prevented the growth of E.G7-OVA tumor in the mouse model. Furthermore, IV injected CO-LDH-215 nanovaccine more effectively delayed tumor growth than that SC injected, largely due to the direct and quick delivery of more nanovaccines to the spleen. This study demonstrates that the therapeutic efficacy of nanovaccines can be greatly enhanced by targeted delivery of nanovaccines to the spleen via the proper vaccination route.

BACKGROUND Probiotics regulate host immune balance, which may reduce immune-related diseases. The effects and mechanisms ofLactobacillus rhamnosus2016SWU.05.0601 (Lr-0601) on the immune response in ovalbumin (OVA)-sensitized mice were explored. RESULTS Lr-0601 reduced serum immunoglobulin (Ig)E and OVA-IgE and attenuated the alteration in lung pathology in OVA-sensitized mice. Lr-0601 blocked OVA-induced up-regulation in serum T helper (Th) 2 and Th17 cytokines but increased the serum levels of Th1 and regulatory T (Treg) cytokines in OVA-sensitized mice. OVA also markedly reduced the protein levels of spleen T-box transcription factor and forkhead/winged helix transcription factor p3, leading to the reduced mRNA expression of interferon-gamma and interleukin (IL)-10. By contrast, OVA markedly increased the protein expression of spleen GATA-binding protein 3 and retinoid-related orphan receptor gamma t, as well as the mRNA expression of spleen IL-4 and IL-17. These changes induced by OVA were reversed by Lr-0601. Moreover, Lr-0601 helped alleviate OVA-induced intestinal microbiota dysbiosis. A correlation was found between specific genera and immune-associated cytokines. CONCLUSION The combined results indicate that Lr-0601 modulated the balance of Th1/Th2 and Treg/Th17 in OVA-sensitized mice, which was associated with the regulation of immune-related transcription factors and gut microbiota. Lr-0601 can potentially be used as a probiotic for preventing immune-related diseases. (c) 2020 Society of Chemical Industry