Splenic-targeting biomimetic nanovaccine for elevating protective immunity against virus infection.

Splenic-targeting biomimetic nanovaccine for elevating protective immunity against virus infection.
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靶向脾脏的仿生纳米疫苗可提高针对病毒感染的保护性免疫力

DOI:
10.1186/s12951-022-01730-0
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发表时间:
2022-12-03
影响因子:
10.2
通讯作者:
He, Hua
He, Hua
中科院分区:
工程技术1区
文献类型:
--
作者:
Huo, Jian;Zhang, Angke;Wang, Shuqi;Cheng, Hanghang;Fan, Daopeng;Huang, Ran;Wang, Yanan;Wan, Bo;Zhang, Gaiping;He, Hua

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病毒性传染病的流行已成为对公共安全、经济社会发展的严重威胁。疫苗一直被认为是通过激活宿主免疫反应来预防病毒传播的最有效平台,但疫苗的免疫原性或安全性低,生产、储存、运输成本高,限制了其有效的临床应用。因此,有必要开发一种有前景的策略来提高疫苗的免疫原性和安全性。我们开发了一种以脾为靶点的仿生纳米疫苗(NV),可以提高对非洲猪瘟病毒(ASFV)感染的保护性体液和细胞免疫。制备了包被甘露糖和CpG(TLR9激动剂)共修饰红细胞膜的通用型PLGA纳米粒(CMR-PLGA/p54 NPs),该纳米粒含有病毒抗原(P54),可作为一种多功能纳米疫苗用于提高保护性免疫。CMR-PLGA/p54 Nvs能被BMDC有效摄取,促进BMDC体外成熟。皮下免疫后,由于RBC的脾归巢能力和甘露糖的DC靶向能力,抗原可以有效地传递到脾树突状细胞(DC),促进抗原提呈和DC成熟,进而诱导更高水平的细胞因子分泌和特异性免疫球蛋白Ig G滴度,CD4+和CD8+T细胞活化和B成熟。此外,NVS在免疫期间表现出显著的安全性。本研究证明了CMR-PLGA纳米粒作为疫苗递送载体在促进体液和细胞免疫应答方面的巨大潜力,并为开发安全有效的病毒感染性疾病疫苗提供了一种有前途的策略。网上版载有补充材料,可在10.1186/s12951-022-01730-0查阅。
The prevalence of viral infectious diseases has become a serious threat to public safety, economic and social development. Vaccines have been served as the most effective platform to prevent virus transmission via the activation of host immune responses, while the low immunogenicity or safety, the high cost of production, storage, transport limit their effective clinical application. Therefore, there is a need to develop a promising strategy to improve the immunogenicity and safety of vaccines. We developed a splenic-targeting biomimetic nanovaccine (NV) that can boost protective humoral and cellular immunity against african swine fever virus (ASFV) infection. The universal PLGA nanoparticles (CMR-PLGA/p54 NPs) coated with mannose and CpG (TLR9 agonist) co-modified red blood cell (RBC) membrane were prepared, which comprised a viral antigen (p54) and can be served as a versatile nanovaccine for elevating protective immunity. CMR-PLGA/p54 NVs could be effectively uptaken by BMDC and promoted BMDC maturation in vitro. After subcutaneous immunization, antigen could be effectively delivered to the splenic dendritic cells (DCs) due to the splenic homing ability of RBC and DC targeting capacity of mannose, which promoted antigen presentation and DCs maturation, and further elicited higher levels of cytokines secretion and specific IgG titers, CD4+ and CD8+ T cells activation and B maturation. Moreover, NVs demonstrated notable safety during the immunization period. This study demonstrates the high potential of CMR-PLGA NPs as vaccine delivery carriers to promote humoral and cellular immune responses, and it provides a promising strategy to develop safe and effective vaccines against viral infectious diseases. The online version contains supplementary material available at 10.1186/s12951-022-01730-0.
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