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BIOMATERIALS · 2024 · IF 12.8

The orientation of CpG conjugation on aluminum oxyhydroxide nanoparticles determines the immunostimulatory effects of combination adjuvants

Zhihui Liang,Hang Bao,Zhiying Yao,Min Li,Chen Chen,Lei Zhang,Huiyang Wang,Yiyang Guo,Yubin Ma,Xuecheng Yang,Ge Yu,Jiancheng Zhang,Changying Xue,Bingbing Sun,Chuanbin Mao

In subunit vaccines, aluminum salts (Alum) are commonly used as adjuvants, but with limited cellular immune responses. To overcome this limitation, CpG oligodeoxynucleotides (ODNs) have been used in combination with Alum. However, current combined usage of Alum and CpG is limited to linear mixtures, and the underlying interaction mechanism between CpG and Alum is not well understood. Thus, we propose to chemically conjugate Alum nanoparticles and CpG (with 5′ or 3′ end exposed) to design combination adjuvants. Our study demonstrates that compared to the 3′-end exposure, the 5′-end exposure of CpG in combination adjuvants (Al-CpG-5′) enhances the activation of bone-marrow derived dendritic cells (BMDCs) and promotes Th1 and Th2 cytokine secretion. We used the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen (HBsAg) as model antigens to demonstrate that Al-CpG-5′ enhanced antigen-specific antibody production and upregulated cytotoxic T lymphocyte markers. Additionally, Al-CpG-5′ allows for coordinated adaptive immune responses even at lower doses of both CpG ODNs and HBsAg antigens, and enhances lymph node transport of antigens and activation of dendritic cells, promoting T fh cell differentiation and B cell activation. Our novel Alum-CPG strategy points the way towards broadening the use of nanoadjuvants for both prophylactic and therapeutic vaccines.

CAS / MDL: 25952-53-8 106627-54-7
研究领域: 免疫学 · 纳米技术 · 疫苗学 · 分子生物学
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Frontiers in Immunology · 2022 · IF 8.786

Bifidobacterium animalis KV9 and Lactobacillus vaginalis FN3 alleviated β-lactoglobulin-induced allergy by modulating dendritic cells in mice

Tian Xiaoying,Fan Rongbo,He Hong,Cui Qingyu,Liang Xi,Liu Qiqi,Liu Tongjie,Lin Kai,Zhang Zhe,Yi Huaxi,Gong Piming,Zhang Lanwei

Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, β-lactoglobulin (β-LG)-sensitized mice were used as models to explore the mechanism of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of β-LG-specific immunoglobulins E (β-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-κB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8−IFN-γ+ T cells in the spleen increased, while CD3+CD8−IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce β-LG-induced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy.

CAS / MDL: 50-23-7
研究领域: 免疫学 · 微生物学 · 过敏学 · 分子生物学
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Engineered Iontophoresis Patch for Epicutaneous Allergen-specific Immunotherapy

Zhiting Cao,Jianye Ren,Yuguan Huang,Tong Li,Zhen Wang,Zhangyi Miao,Jia Jia,Yang Ding

Epidermal immunotherapy represents an emerging treatment method for allergic diseases. Nevertheless, an unformidable obstacle for epidermal drug delivery is the dense stratum corneum of the skin. Here, iontophoresis technology is utilized for epidermal delivery of allergen protein. Briefly, an iontophoresis patch consists of conductive nanofiber polypyrrole (PPy) and polyvinyl alcohol (PVA) by electrospinning technology, onto which cationic lipid dioctadecyl–dimethylammonium bromide vesicles containing ovalbumin (DDA@OVA) are loaded via electrospraying technology, forming a stable in situ composite structure. Compared with DDA@OVA/PVA, DDA@OVA/PPy-PVA demonstrated a significant increase in both allergen release and penetration into the epidermis. Ultimately, a high-level activation of antigen-presenting cells is facilitated. Importantly, DDA@OVA/PPy-PVA induces a significant increase in the levels of helper T cell 1 (Th1)-related cytokines such as IFN-γ and IL-12, inhibits the differentiation of T cells into Th2 cells, and further affects the secretion of OVA-specific IgE and promotes the production of protective antibody IgG. The lung tissue analysis illustrates that DDA@OVA/PPy-PVA treatment achieves regular alveolar structures in the lumen and significantly relieved asthma symptoms. The findings indicate that iontophoresis patches provide multiple benefits, including drug-responsive release, efficient penetration, and advanced therapeutic efficacy. These attributes make iontophoresis patches a promising treatment option for allergic diseases.

研究领域: 生物医学工程 · 药学 · 免疫学 · 过敏研究 · 药物递送系统 · 纳米技术 · 材料科学 · 呼吸系统疾病
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