A self-assembling nanoparticle: Implications for the development of thermostable vaccine candidates

被引：19
作者：
Liu, Ze-Hui [1 ]
Xu, Hui-Ling [1 ]
Han, Guang-Wei [1 ]
Tao, Li-Na [1 ]
Lu, Ying [1 ]
Zheng, Su-Ya [1 ]
Fang, Wei-Huan [1 ,2 ]
He, Fang [1 ,2 ]
机构：
[1] Zhejiang Univ, Coll Anim Sci, Inst Prevent Vet Med, 866 Yuhangtang Rd, Hangzhou 310058, Peoples R China
[2] Zhejiang Prov Key Lab Prevent Vet Med, Hangzhou 310058, Peoples R China
来源：
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES | 2021年 / 183卷
关键词：
Self-assembling nanoparticle; Nanovaccine; Enhanced immunogenicity; VIRUS-LIKE PARTICLES; CLASSICAL SWINE-FEVER; IN-VITRO; DELIVERY; DESIGN; SIZE; IMMUNOGENICITY; MECHANISMS; RESPONSES; ANTIGENS;
D O I：
10.1016/j.ijbiomac.2021.06.024
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Effective controls on viral infections rely on the continuous development in vaccine technology. Nanoparticle (NP) antigens are highly immunogenic based on their unique physicochemical properties, making them molecular scaffolds to present soluble vaccine antigens. Here, viral targets (113-354 aas) were genetically fused to N terminal of mi3, a protein that self-assembles into nanoparticles composed of 60 subunits. With transmission electron microscopy, it was confirmed that target-mi3 fusion proteins which have insertions of up to 354 aas in N terminal form intact NPs. Moreover, viral targets are surface-displayed on NPs as indicated in dynamic light scattering. NPs exhibit perfect stability after long-term storage at room temperature. Moreover, SP-E2-mi3 NPs enhance antigen uptake and maturation in dendritic cells (DCs) via up-regulating marker molecules and immunostimulatory cytokines. Importantly, in a mouse model, SP-E2-mi3 nanovaccines against Classical swine fever virus (CSFV) remarkably improved CSFV-specific neutralizing antibodies (NAbs) and cellular immunity related cytokines (IFN-gamma and IL-4) as compared to monomeric E2. Specially, improved NAb response with more than tenfold increase in NAb titer against both CSFV Shimen and HZ-08 strains indicated better cross-protection against different genotypes. Collectively, this structure-based, self-assembling NP provides an attractive platform to improve the potency of subunit vaccine for emerging pathogens.
引用
收藏
页码：2162 / 2173
页数：12
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