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可誘導(dǎo)針對(duì)新冠病毒變異株廣譜中和抗體應(yīng)答的新冠候選納米顆粒疫苗作用機(jī)制

更新時(shí)間:2026-06-27   點(diǎn)擊次數(shù):266次

中文摘要:

能夠誘導(dǎo)強(qiáng)效中和抗體(NAb)應(yīng)答、靶向新型嚴(yán)重急性呼吸綜合征冠狀病毒 2(SARS-CoV-2)變異株的疫苗,是抗擊 2019 冠狀病毒病大流行的關(guān)鍵。本研究證實(shí),采用自組裝蛋白納米顆粒(SApNP)免疫小鼠后產(chǎn)生的血漿可有效中和 B.1.1.7、B.1.351、P.1 及 B.1.617 變異株,中和效力相當(dāng);該納米顆粒表面精準(zhǔn)展示 20 株經(jīng)理性設(shè)計(jì)的武漢原始株 Wuhan-Hu-1 刺突蛋白 S2GΔHR2。

本研究針對(duì)多層結(jié)構(gòu) I3-01v9 自組裝蛋白納米顆粒設(shè)計(jì) 16 種制劑配方,探究佐劑對(duì)疫苗誘導(dǎo)免疫應(yīng)答的增效作用。通過(guò)單細(xì)胞分選技術(shù),分別從受體結(jié)合域(RBD)、S2GΔHR2 刺突蛋白、自組裝蛋白納米顆粒疫苗免疫小鼠體內(nèi)分離得到一批中和廣度與中和效力各異的單克隆抗體(mAb),并借助小鼠模型解析該疫苗誘導(dǎo)免疫應(yīng)答的作用機(jī)制。

相較于可溶性刺突蛋白,I3-01v9 自組裝蛋白納米顆粒具備以下優(yōu)勢(shì):體內(nèi)留存時(shí)間延長(zhǎng) 6 倍,濾泡樹(shù)突狀細(xì)胞突起上的抗原呈遞量提升 4 倍,淋巴結(jié)濾泡生發(fā)中心反應(yīng)強(qiáng)度增強(qiáng) 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.


論文信息:

論文題目:Mechanism of a coronavirus nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants

期刊名稱(chēng):Science Advances

時(shí)間期卷:Vol 7, Issue43(2021)

在線時(shí)間:2021年10月20日

DOI: 10.1126/sciadv.abj3107

產(chǎn)品信息:

貨號(hào):CP-005-005

規(guī)格:5ml+5ml

品牌:Liposoma

產(chǎn)地:荷蘭

名稱(chēng):Clodronate Liposomes&Control Liposomes

辦事處:靶點(diǎn)科技


Clodronate Liposomes氯膦酸鹽脂質(zhì)體皮內(nèi)注射,清除淋巴結(jié)被膜下竇巨噬細(xì)胞。荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見(jiàn)刊于Science Advances:可誘導(dǎo)針對(duì)新冠病毒變異株廣譜中和抗體應(yīng)答的新冠候選納米顆粒疫苗作用機(jī)制。

可誘導(dǎo)針對(duì)新冠病毒變異株廣譜中和抗體應(yīng)答的新冠候選納米顆粒疫苗作用機(jī)制




Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)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.

采用巨噬細(xì)胞清除脂質(zhì)體抑制劑 CLs(Liposoma BV,貨號(hào) CP-005-005)清除淋巴結(jié)被膜下竇巨噬細(xì)胞,以此增強(qiáng) B 細(xì)胞活化水平。



巨噬細(xì)胞清除材料和方法文獻(xiàn)截圖:可誘導(dǎo)針對(duì)新冠病毒變異株廣譜中和抗體應(yīng)答的新冠候選納米顆粒疫苗作用機(jī)制

可誘導(dǎo)針對(duì)新冠病毒變異株廣譜中和抗體應(yīng)答的新冠候選納米顆粒疫苗作用機(jī)制




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