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Intranasal vaccination with influenza HA/GO-PEI nanoparticles provides immune protection against homo- and heterologous strains [Immunology and Inflammation]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2021-05-11 , DOI: 10.1073/pnas.2024998118
Chunhong Dong, Ye Wang, Gilbert X. Gonzalez, Yao Ma, Yufeng Song, Shelly Wang, Sang-Moo Kang, Richard W. Compans, Bao-Zhong Wang

Intranasal (i.n.) immunization is a promising vaccination route for infectious respiratory diseases such as influenza. Recombinant protein vaccines can overcome the safety concerns and long production phase of virus-based influenza vaccines. However, soluble protein vaccines are poorly immunogenic if administered by an i.n. route. Here, we report that polyethyleneimine-functionalized graphene oxide nanoparticles (GP nanoparticles) showed high antigen-loading capacities and superior immunoenhancing properties. Via a facile electrostatic adsorption approach, influenza hemagglutinin (HA) was incorporated into GP nanoparticles and maintained structural integrity and antigenicity. The resulting GP nanoparticles enhanced antigen internalization and promoted inflammatory cytokine production and JAWS II dendritic cell maturation. Compared with soluble HA, GP nanoparticle formulations induced significantly enhanced and cross-reactive immune responses at both systemic sites and mucosal surfaces in mice after i.n. immunization. In the absence of any additional adjuvant, the GP nanoparticle significantly boosted antigen-specific humoral and cellular immune responses, comparable to the acknowledged potent mucosal immunomodulator CpG. The robust immune responses conferred immune protection against challenges by homologous and heterologous viruses. Additionally, the solid self-adjuvant effect of GP nanoparticles may mask the role of CpG when coincorporated. In the absence of currently approved mucosal adjuvants, GP nanoparticles can be developed into potent i.n. influenza vaccines, providing broad protection. With versatility and flexibility, the GP nanoplatform can be easily adapted for constructing mucosal vaccines for different respiratory pathogens.



中文翻译:

流感HA / GO-PEI纳米粒子的鼻内疫苗接种可提供针对同种和异种菌株的免疫保护[免疫学和炎症]

鼻内(in)免疫是一种用于传染性呼吸道疾病(例如流感)的有希望的疫苗接种途径。重组蛋白疫苗可以克服基于病毒的流感疫苗的安全性问题和较长的生产阶段。但是,如果通过途径给药,可溶性蛋白疫苗的免疫原性很差。在这里,我们报告聚乙烯亚胺官能化的氧化石墨烯纳米颗粒(GP纳米颗粒)显示出高的抗原负载能力和优异的免疫增强性能。通过简便的静电吸附方法,将流感血凝素(HA)掺入GP纳米颗粒中并保持结构完整性和抗原性。所得的GP纳米颗粒增强了抗原的内在化,并促进了炎症细胞因子的产生和JAWS II树突状细胞的成熟。与可溶性HA相比,免疫后,GP纳米颗粒制剂在小鼠的全身部位和粘膜表面均诱导明显增强的交叉反应性免疫反应。在没有任何其他佐剂的情况下,GP纳米颗粒可显着增强抗原特异性的体液和细胞免疫应答,与公认的强效粘膜免疫调节剂CpG相当。强大的免疫应答赋予免疫保护以抵抗同源和异源病毒的攻击。此外,GP纳米粒子的固体自佐剂作用可能会掩盖CpG在合并时的作用。在目前尚无批准的粘膜佐剂的情况下,GP纳米颗粒可发展成为对流感疫苗有效的疫苗,可提供广泛的保护。具有多功能性和灵活性,

更新日期:2021-05-03
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