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可诱导针对新冠病毒变异株广谱中和抗体应答的新冠候选纳米颗粒疫苗作用机制

更新时间:2026-06-27   点击次数:47次

中文摘要:

能够诱导强效中和抗体(NAb)应答、靶向新型严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)变异株的疫苗,是抗击 2019 冠状病毒病大流行的关键。本研究证实,采用自组装蛋白纳米颗粒(SApNP)免疫小鼠后产生的血浆可有效中和 B.1.1.7、B.1.351、P.1 及 B.1.617 变异株,中和效力相当;该纳米颗粒表面精准展示 20 株经理性设计的武汉原始株 Wuhan-Hu-1 刺突蛋白 S2GΔHR2。

本研究针对多层结构 I3-01v9 自组装蛋白纳米颗粒设计 16 种制剂配方,探究佐剂对疫苗诱导免疫应答的增效作用。通过单细胞分选技术,分别从受体结合域(RBD)、S2GΔHR2 刺突蛋白、自组装蛋白纳米颗粒疫苗免疫小鼠体内分离得到一批中和广度与中和效力各异的单克隆抗体(mAb),并借助小鼠模型解析该疫苗诱导免疫应答的作用机制。

相较于可溶性刺突蛋白,I3-01v9 自组装蛋白纳米颗粒具备以下优势:体内留存时间延长 6 倍,滤泡树突状细胞突起上的抗原呈递量提升 4 倍,淋巴结滤泡生发中心反应强度增强 5 倍。



英文摘要:

Vaccines that induce potent neutralizing antibody (NAb) responses against emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for combating the coronavirus disease 2019 pandemic. We demonstrated that mouse plasma induced by self-assembling protein nanoparticles (SApNPs) that present 20 rationally designed S2GΔHR2 spikes of the ancestral Wuhan-Hu-1 strain can neutralize the B.1.1.7, B.1.351, P.1, and B.1.617 variants with comparable potency. The adjuvant effect on vaccine-induced immunity was investigated by testing 16 formulations for the multilayered I3-01v9 SApNP. Using single-cell sorting, monoclonal antibodies (mAbs) with diverse neutralization breadth and potency were isolated from mice immunized with the receptor binding domain (RBD), S2GΔHR2 spike, and SApNP vaccines. The mechanism of vaccine-induced immunity was examined in the mouse model. Compared with the soluble spike, the I3-01v9 SApNP showed sixfold longer retention, fourfold greater presentation on follicular dendritic cell dendrites, and fivefold stronger germinal center reactions in lymph node follicles.


论文信息:

论文题目:Mechanism of a coronavirus nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants

期刊名称:Science Advances

时间期卷:Vol 7, Issue43(2021)

在线时间:2021年10月20日

DOI: 10.1126/sciadv.abj3107

产品信息:

货号:CP-005-005

规格:5ml+5ml

品牌:Liposoma

产地:荷兰

名称:Clodronate Liposomes&Control Liposomes

办事处:靶点科技


Clodronate Liposomes氯膦酸盐脂质体皮内注射,清除淋巴结被膜下窦巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances:可诱导针对新冠病毒变异株广谱中和抗体应答的新冠候选纳米颗粒疫苗作用机制。

可诱导针对新冠病毒变异株广谱中和抗体应答的新冠候选纳米颗粒疫苗作用机制




Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法:

In vivo macrophage depletion

Macrophage inhibitor CLs (Liposoma BV, catalog no. CP-005-005) were used to eliminate subcapsular sinus macrophages in lymph nodes to promote more robust B cell activation.

采用巨噬细胞清除脂质体抑制剂 CLs(Liposoma BV,货号 CP-005-005)清除淋巴结被膜下窦巨噬细胞,以此增强 B 细胞活化水平。



巨噬细胞清除材料和方法文献截图:可诱导针对新冠病毒变异株广谱中和抗体应答的新冠候选纳米颗粒疫苗作用机制

可诱导针对新冠病毒变异株广谱中和抗体应答的新冠候选纳米颗粒疫苗作用机制




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