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载核酸的双重协同壳聚糖包覆的聚(乳酸-共-乙醇酸)纳米球作为鼻腔内给药疫苗传递系统控制口蹄疫病毒感染。

Double synergic chitosan-coated poly (lactic-co-glycolic) acid nanospheres loaded with nucleic acids as an intranasally administered vaccine delivery system to control the infection of foot-and-mouth disease virus.

机构信息

State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.

State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, National Foot-and-Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China; Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.

出版信息

Antiviral Res. 2024 Jun;226:105900. doi: 10.1016/j.antiviral.2024.105900. Epub 2024 May 4.

Abstract

BACKGROUND & AIMS: The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial.

PATIENTS AND METHODS

Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs).

RESULTS

The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs.

CONCLUSIONS

The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.

摘要

背景与目的

口蹄疫病毒(FMDV)通过气溶胶飞沫在密切接触的偶蹄动物中传播,这是畜牧业成功的主要障碍。因此,开发合适的黏膜疫苗,特别是鼻内疫苗,以在病毒感染的初始部位阻断病毒至关重要。

患者和方法

在这里,我们构建了含有 FMDV T 和 B 细胞表位(pTB)与分子黏膜佐剂 Fms 样酪氨酸激酶受体 3 配体(Flt3 配体,FL)(pTB-FL)串联的真核表达质粒。然后,将构建的质粒静电附着到甘露糖修饰壳聚糖包裹的聚乳酸-共-羟基乙酸(PLGA)纳米球(MCS-PLGA-NPs)上,以获得针对抗原呈递细胞(APCs)表面甘露糖受体的靶向性鼻内疫苗。

结果

负载 pTB-FL 的 MCS-PLGA-NPs 不仅诱导了局部黏膜免疫应答,还诱导了小鼠的全身免疫应答。更重要的是,当该鼻内疫苗被皮下注射到豚鼠脚底时,可提供对高毒力 FMDV 株(AF72)80%的保护率。

结论

本研究制备的鼻内疫苗可有效诱导针对同型 FMDV 挑战的交叉保护免疫应答,有望成为一种潜在的 FMDV 疫苗。

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