Hexahistidine-Metal Assemblies: A Facile and Effective Codelivery System of Subunit Vaccines for Potent Humoral and Cellular Immune Responses.,Molecular Pharmaceutics

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Hexahistidine-Metal Assemblies: A Facile and Effective Codelivery System of Subunit Vaccines for Potent Humoral and Cellular Immune Responses.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-05-29 , DOI: 10.1021/acs.molpharmaceut.0c00212
Tinghong Zhang _{1,

2} , Long Zhang ₂ , Xiaoxiao Wu ₁ , Hongyan Xu ₁ , Pengyan Hao ₁ , Wenjuan Huang ₁ , Yagang Zhang ₃ , Xingjie Zan _{1,

2}

Affiliation

Fully effective vaccines must induce both potent humoral and cellular immunities. Nanoparticles coencapsulating antigens and adjuvants have shown promising advantages as subunit vaccines in many aspects. However, the low loading efficiency and complicated synthesis process of these nanomaterials need to be improved. Here, we utilized hexahistidine (His₆)–metal assembly (HmA) particles as carriers to codeliver ovalbumin peptides and cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs). We found that antigen/adjuvant-carrying HmA can efficiently enter into antigen-presenting cells and help the antigens escape from lysosomes to induce the maturation of these cells in vitro, characterized by increasing expression levels of costimulatory molecules and cytokines. More importantly, the vaccines with high biocompatibility can elicit strong humoral and cellular immunities by improving secretion of specific antibodies and cytokines, enhancing activation of DCs and T cells in vivo. Our results suggest that HmA provides a new approach for subunit vaccines by codelivery of antigens and adjuvants.

中文翻译：

六组氨酸-金属装配体：用于有效的体液和细胞免疫反应的亚单位疫苗的简便有效的代码传递系统。

完全有效的疫苗必须诱导有效的体液和细胞免疫。共封装抗原和佐剂的纳米颗粒在许多方面显示出作为亚单位疫苗的有希望的优势。然而，这些纳米材料的低负载效率和复杂的合成过程需要改进。在这里，我们利用六组氨酸（His ₆）-金属组装（HmA）颗粒作为载体来编码卵清蛋白肽和胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸（CpG ODN）。我们发现携带抗原/佐剂的HmA可以有效进入抗原呈递细胞，并帮助抗原从溶酶体中逃逸，从而诱导这些细胞在体外成熟，其特点是增加了共刺激分子和细胞因子的表达水平。更重要的是，具有高生物相容性的疫苗可以通过改善特异性抗体和细胞因子的分泌，增强体内DC和T细胞的活化来引发强烈的体液和细胞免疫。我们的结果表明，HmA通过抗原和佐剂的代码传递为亚单位疫苗提供了一种新方法。

更新日期：2020-07-06

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