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镁/铝层状双氢氧化物作为百日咳疫苗的纳米佐剂:与氢氧化铝佐剂的比较评估。

Mg/Al-LDH as a nano-adjuvant for pertussis vaccine: a evaluation compared with aluminum hydroxide adjuvant.

机构信息

National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, No. 2699 Qianjin Street, Changchun 130012, People's Republic of China.

School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, No. 26, Huatuo Street, Benxi 117004, People's Republic of China.

出版信息

Nanotechnology. 2022 Mar 17;33(23). doi: 10.1088/1361-6528/ac56f3.

DOI:10.1088/1361-6528/ac56f3
PMID:35189608
Abstract

. Layered double hydroxide (LDH) has been demonstrated as a highly efficient antigen platform to induce effective and durable immune response. However, whether LDH nanoparticles could act as an adjuvant for pertussis vaccines is still unknown. Here we evaluated the potential of Mg/Al-LDH as a nano-adjuvant to improve immune response against pertussis and compared it with commercial aluminum hydroxide (AH) adjuvant.. The Mg/Al-LDH nanoparticles were synthesized by a hydrothermal reaction. The morphology, structure and size of Mg/Al-LDH were characterized by transmission electron microscope, x-ray diffraction and MALVERN particle analysis. The ovalbumin and Pertussis toxin (PTd) was adsorbed to Mg/Al-LDH. The immune response of antigen-LDH complex was evaluated in mice, compared with commercial adjuvant alum. Hematoxylin-eosin staining was used to evaluate the inflammatory response at injection site.. The synthetic Mg/Al-LDH nanoparticles showed a typical hexagonal lamellar structure. The average size of synthetic nanoparticles was 102.9 nm with PDI of 0.13 and zeta potential was 44.4 mV. Mg/Al-LDH nanoparticles effectively adsorbed protein antigen and mediated antigen uptake by DC cells. Animal experiments showed that Mg/Al-LDH gave enhancement in anti-pertussis toxin (PTd) humoral immune response, which was considerable to commercial AH adjuvant. Finally, Mg/Al-LDH produced a slighter inflammatory response than AH at injection site and this injury was quickly recovered.. Our study demonstrated the potential of Mg/Al-LDH as an effective adjuvant for pertussis vaccine, which induced comparable antibody response and had a better safety compared with commercial AH adjuvant.

摘要

层状双氢氧化物(LDH)已被证明是一种高效的抗原平台,可诱导有效的、持久的免疫反应。然而,LDH 纳米颗粒是否可以作为百日咳疫苗的佐剂尚不清楚。在这里,我们评估了 Mg/Al-LDH 作为纳米佐剂的潜力,以提高对百日咳的免疫反应,并将其与商业氢氧化铝(AH)佐剂进行了比较。Mg/Al-LDH 纳米颗粒通过水热反应合成。通过透射电子显微镜、X 射线衍射和马尔文粒度分析对 Mg/Al-LDH 的形态、结构和尺寸进行了表征。卵清蛋白和百日咳毒素(PTd)被吸附到 Mg/Al-LDH 上。在小鼠中评估了抗原-LDH 复合物的免疫反应,并与商业佐剂明矾进行了比较。苏木精-伊红染色用于评估注射部位的炎症反应。合成的 Mg/Al-LDH 纳米颗粒呈现出典型的六方层状结构。合成纳米颗粒的平均尺寸为 102.9nm,PDI 为 0.13,zeta 电位为 44.4mV。Mg/Al-LDH 纳米颗粒有效地吸附了蛋白抗原,并介导了 DC 细胞对抗原的摄取。动物实验表明,Mg/Al-LDH 增强了抗百日咳毒素(PTd)体液免疫反应,与商业 AH 佐剂相当。最后,与 AH 相比,Mg/Al-LDH 在注射部位产生的炎症反应较轻,这种损伤很快得到恢复。我们的研究表明,Mg/Al-LDH 作为百日咳疫苗的有效佐剂具有潜力,与商业 AH 佐剂相比,它能诱导相当的抗体反应,并具有更好的安全性。

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