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二氧化硅纳米颗粒作为使用乙肝核心病毒样颗粒对小鼠进行免疫接种的佐剂。

Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.

作者信息

Skrastina Dace, Petrovskis Ivars, Lieknina Ilva, Bogans Janis, Renhofa Regina, Ose Velta, Dishlers Andris, Dekhtyar Yuri, Pumpens Paul

机构信息

Latvian Biomedical Research and Study Centre, Riga, Latvia.

Institute of Biomedical Engineering and Nanotechnologies, Riga Technical University, Riga, Latvia.

出版信息

PLoS One. 2014 Dec 1;9(12):e114006. doi: 10.1371/journal.pone.0114006. eCollection 2014.

Abstract

Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm) with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs) formed by recombinant full-length Hepatitis B virus core (HBc) protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL) led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.

摘要

纳米技术和纳米材料的进步推动了二氧化硅(SiO₂)颗粒作为一种有前景的免疫佐剂的发展,用于开发新型预防性和治疗性疫苗。在本研究中,我们比较了市售二氧化硅纳米颗粒(初始粒径为10-20nm)与氢氧化铝(明矾)以及完全和不完全弗氏佐剂在辅助用重组全长乙型肝炎病毒核心(HBc)蛋白形成的病毒样颗粒(VLP)免疫BALB/c小鼠方面的潜力。免疫后研究了B细胞和T细胞反应的诱导情况。二氧化硅纳米颗粒能够最大程度地吸附40%添加的HBc,而在相同的VLP/佐剂比例下,明矾的吸附能力超过90%。通过动态光散射、分光光度法和电子显微镜检测发现,二氧化硅和明矾都与HBc VLP形成了大的复合物,在配制后迅速沉淀。在腹腔内免疫的情况下,二氧化硅和明矾都增强了针对HBc VLP的体液反应,使其达到高抗HBc水平,而在皮下免疫中,二氧化硅佐剂的抗HBc水平甚至超过了明矾佐剂的水平。二氧化硅对HBc VLP的佐剂作用导致与明矾佐剂情况相同的典型IgG2a/IgG1比率。二氧化硅与单磷酰脂质A(MPL)的组合导致与明矾和MPL组合情况相同的HBc特异性T细胞诱导增强。这些发现表明,在诱导针对重组HBc VLP的B细胞和T细胞反应方面,二氧化硅并非比明矾弱的假定佐剂。这一发现可能对基于一系列HBc衍生的病毒样颗粒作为生物成分的二氧化硅佐剂疫苗的开发产生重要影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4778/4250084/367e8e4b45f0/pone.0114006.g001.jpg

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