In this investigation, to maximize the desired immunoenhancement effects of PsEUL and stimulate an efficient humoral and cellular immune response against an antigen, PsEUL and the model antigen ovalbumin (OVA) were coupled using the N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) reaction to yield a novel delivery system (PsEUL-OVA). The physicochemical characteristics and immune regulation effects of this new system were investigated. We found the yield of this EDC method to be 46.25%. In vitro, PsEUL-OVA (200 μg mL−1) could enhance macrophage proliferation and increase their phagocytic efficiency. In vivo, PsEUL-OVA could significantly increase the levels of OVA-specific antibody (IgG, IgG1, IgG2a, and IgG2b) titers and cytokine (IL-2, IL-4, IL-6, IFN-γ) levels. Additionally, it could activate T lymphocytes and facilitate the maturation of dendritic cells (DCs). These findings collectively suggested that PsEUL-OVA induced humoral and cellular immune responses by promoting the phagocytic activity of macrophages and DCs. Taken together, these results revealed that PsEUL-OVA had the potential to improve immune responses and provide a promising theoretical basis for the design of a novel delivery system.

The mannose receptor (MAN-R)-targeted delivery system is commonly used to deliver antigens to macrophages or immature dendritic cells (DCs) to promote the efficiency of antigen presentation. To maximize the enhancement effects of chitosan (CS) and induce an efficient humoral and cellular immune response against an antigen, we encapsulated ovalbumin (OVA) in poly(lactic-co-glycolic acid) (PLGA) microspheres (MPs) and conjugated it with MAN-modified CS to obtain MAN-R-targeting nano-MPs (MAN-CS-OVA-PLGA-MPs). The physicochemical properties, drug loading rate, and immunomodulation activity of MAN-CS-OVA-PLGA-MPs were evaluated. In vitro, MAN-CS-OVA-PLGA-MPs (80 μg mL−1) could enhance the proliferation of DCs and increase their phagocytic efficiency. In vivo, MAN-CS-OVA-PLGA-MPs significantly increased the ratio of CD3+CD4+/CD3+CD8+ T cells, increased CD80+, CD86+, and MHC II expression in DCs, and improved OVA-specific IgG, IgG1, IgG2a, and IgG2b antibodies. Moreover, MAN-CS-OVA-PLGA-MPs promoted cytokine (IFN-γ, IL-4, and IL-6) production in mice. Taken together, our results show that MAN-CS-OVA-PLGA-MPs may act by activating the T cells to initiate an immune response by promoting the maturation of dendritic cells and improving their antigen presentation efficiency. The current study provides a basis for the use of MAN-CS-OVA-PLGA-MPs as an antigen and adjuvant delivery system targeting the MAN-R on the surface of macrophages and dendritic cells.

Carbon nanotubes (CNTs) are carbon allotropes consisting of one, two, or more concentric rolled graphene layers. These can intrinsically regulate immunity by activating the innate immune system. Mannose receptors (MR), a subgroup of the C-type lectin superfamily, are abundantly expressed on macrophages and dendritic cells. These play a crucial role in identifying pathogens, presenting antigens, and maintaining internal environmental stability. Utilizing the specific recognition between mannose and antigen-presenting cells (APC) surface mannose receptors, the antigen-carrying capacity of mannose-modified CNTs can be improved. Accordingly, here, we synthesized the mannose-modified carbon nanotubes (M-MWCNT) and evaluated them as an antigen delivery system through a series of in vitro and in vivo experiments. In vitro, M-MWCNT carrying large amounts of OVA were rapidly phagocytized by macrophages and promoted macrophage proliferation to facilitate cytokines (IL-1β, IL-6) secretion. In vivo, in mice, M-MWCNT induced the maturation of dendritic cells and increased the levels of antigen-specific antibodies (IgG, IgG1, IgG2a, IgG2b), and cytokines (IFN-γ, IL-6). Taken together, M-MWCNT could induce both humoral and cellular immune responses and thereby can be utilized as an efficient antigen-targeted delivery system.

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BACKGROUND: To improve the adjuvant activity of polysaccharides from Eucommia ulmoides leaves (PsEUL) in inducing an effective immune response against ovalbumin (OVA), PsEUL were conjugated to OVA using the N-(3-dimethylaminopropyl)-N 0 -ethylcarbodiimide hydrochloride (EDC) method. The synthesized PsEUL-OVA was encapsulated using phytantriol and F127 to produce PsEUL-OVA cubosomes (Cubs), a novel delivery system. The physicochemical properties and immune modulation effects of this novel delivery system were explored. RESULTS:In vitro, PsEUL-OVA/Cubs carrying large amounts of OVA were rapidly phagocytized by macrophages and upregulated macrophage proliferation, thereby stimulating cytokine production (interleukin (IL)-6 and IL-4). In vivo, PsEUL-OVA/Cubs increased the titer of OVA-specific antibodies (immunoglobulin (Ig)G, IgG2b, IgG2a and IgG1) and cytokine levels (IL-2, IL-6, IL-4 and interferon-γ). In addition, the cubosomes promoted the differentiation of CD8 + and CD4 + T cells in the spleen and the maturation of dendritic cells (DCs). These results indicated that PsEUL-OVA/Cubs stimulated both cellular and humoral immune responses by enhancing the phagocytic activity of DCs and macrophages and increasing the antigen presentation efficiency. CONCLUSION: Collectively, the findings demonstrate that PsEUL-antigen/Cubs can be a useful delivery vehicle with immune response-promoting effects. Therefore, this study lays the foundation for the development of novel adjuvant-antigen delivery systems with potential applications in vaccine design.