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Intranasal Nanovaccine Confers Homo‐ and Hetero‐Subtypic Influenza Protection
Small ( IF 13.0 ) Pub Date : 2018-02-12 , DOI: 10.1002/smll.201703207
Mi Qi 1 , Xian-En Zhang 2 , Xianxun Sun 1 , Xiaowei Zhang 1 , Yanfeng Yao 3 , Siling Liu 4 , Ze Chen 5 , Wei Li 1 , Zhiping Zhang 1 , Jianjun Chen 4 , Zongqiang Cui 1
Affiliation  

Cross‐protective and non‐invasively administered vaccines are attractive and highly desired for the control of influenza. Self‐assembling nanotechnology provides an opportunity for the development of vaccines with superior performance. In this study, an intranasal nanovaccine is developed targeting the conserved ectodomain of influenza matrix protein 2(M2e). 3‐sequential repeats of M2e (3M2e) is presented on the self‐assembling recombinant human heavy chain ferritin (rHF) cage to form the 3M2e‐rHF nanoparticle. Intranasal vaccination with 3M2e‐rHF nanoparticles in the absence of an adjuvant induces robust immune responses, including high titers of sera M2e‐specific IgG antibodies, T‐cell immune responses, and mucosal secretory‐IgA antibodies in mice. The 3M2e‐rHF nanoparticles also confer complete protection against a lethal infection of homo‐subtypic H1N1 and hetero‐subtypic H9N2 virus. An analysis of the mechanism of protection underlying the intranasal immunization with the 3M2e‐rHF nanoparticle indicates that M2e‐specific mucosal secretory‐IgA and T‐cell immune responses may play critical roles in the prevention of infection. The results suggest that the 3M2e‐rHF nanoparticle is a promising, needle‐free, intranasally administered, cross‐protective influenza vaccine. The use of self‐assembling nanovaccines could be an ideal strategy for developing vaccines with characteristics such as high immunogenicity, cross‐protection, and convenient administration, as well as being economical and suitable for large‐scale production.

中文翻译:

鼻内纳米疫苗赋予人和亚型流感的保护

交叉保护性和非侵入性管理的疫苗对于控制流感很有吸引力,并且非常需要。自组装纳米技术为开发性能卓越的疫苗提供了机会。在这项研究中,开发了针对流感基质蛋白2(M2e)保守胞外域的鼻内纳米疫苗。M2e(3M2e)的3个序列重复序列出现在自组装的重组人重链铁蛋白(rHF)笼子上,形成3M2e-rHF纳米颗粒。在没有佐剂的情况下用3M2e-rHF纳米粒子进行鼻内疫苗接种可诱导强大的免疫反应,包括高滴度的M2e特异性血清IgG抗体,T细胞免疫反应和小鼠黏膜分泌IgA抗体。3M2e-rHF纳米颗粒还具有完全保护作用,可抵抗同型亚型H1N1和异型亚型H9N2病毒的致死性感染。对使用3M2e-rHF纳米颗粒进行鼻内免疫的保护机制的分析表明,M2e特异性粘膜分泌IgA和T细胞免疫应答在预防感染中可能起关键作用。结果表明3M2e-rHF纳米颗粒是一种有前途的,无针,鼻内给药的交叉保护型流感疫苗。自组装纳米疫苗的使用可能是开发具有高免疫原性,交叉保护,易于管理,经济且适合大规模生产的特征的疫苗的理想策略。对使用3M2e-rHF纳米颗粒进行鼻内免疫的保护机制的分析表明,M2e特异性粘膜分泌IgA和T细胞免疫应答在预防感染中可能起关键作用。结果表明3M2e-rHF纳米颗粒是一种有前途的,无针,鼻内给药的交叉保护型流感疫苗。自组装纳米疫苗的使用可能是开发具有高免疫原性,交叉保护,易于管理,经济且适合大规模生产的特征的疫苗的理想策略。对使用3M2e-rHF纳米颗粒进行鼻内免疫的保护机制的分析表明,M2e特异性粘膜分泌IgA和T细胞免疫应答在预防感染中可能起关键作用。结果表明3M2e-rHF纳米颗粒是一种有前途的,无针,鼻内给药的交叉保护型流感疫苗。自组装纳米疫苗的使用可能是开发具有高免疫原性,交叉保护,易于管理,经济且适合大规模生产的特征的疫苗的理想策略。
更新日期:2018-02-12
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