Design of a stabilized RBD enables potently neutralizing SARS-CoV-2 single-component nanoparticle vaccines.
Design of a stabilized RBD enables potently neutralizing SARS-CoV-2 single-component nanoparticle vaccines.
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DOI：
10.1016/j.celrep.2023.112266
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发表时间：
2023-03-28
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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免疫力下降和新出现的变异需要继续接种针对严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的疫苗。提高疫苗的安全性、耐受性和生产的便利性将有利于这些努力。在这里，我们开发了一种有效且易于制造的纳米颗粒疫苗，显示刺突受体结合域（RBD）。通过计算设计来稳定RBD，消除糖基化，并将免疫反应集中在中和的表位上，从而产生RBD免疫原，解决了阻碍天然RBD高效纳米颗粒展示的问题。这种非糖基化RBD可以基因融合到不同的单组分纳米颗粒平台上，最大限度地提高了制造的便利性和灵活性。所有工程化的RBD纳米颗粒在小鼠体内引发的强效中和抗体远远超过单体RBD。一个60拷贝的粒子（noNAG-RBD-E2p）也在非人灵长类动物中引发了强有力的中和抗体。noNAG-RBD-E2p引发的中和抗体滴度与基准稳定刺突抗原相当，并达到针对Omicron BA.5的水平，这表明它可以提供对新出现变体的保护。SARS-CoV-2 RBD疫苗具有成本效益，但需要提高其效力的方法。Dickey等人使用计算设计方法创建了一种稳定的非糖基化RBD，可以融合到纳米颗粒载体上，将其效力提高到金标准刺突抗原的水平。
Waning immunity and emerging variants necessitate continued vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Improvements in vaccine safety, tolerability, and ease of manufacturing would benefit these efforts. Here, we develop a potent and easily manufactured nanoparticle vaccine displaying the spike receptor-binding domain (RBD). Computational design to stabilize the RBD, eliminate glycosylation, and focus the immune response to neutralizing epitopes results in an RBD immunogen that resolves issues hindering the efficient nanoparticle display of the native RBD. This non-glycosylated RBD can be genetically fused to diverse single-component nanoparticle platforms, maximizing manufacturing ease and flexibility. All engineered RBD nanoparticles elicit potently neutralizing antibodies in mice that far exceed monomeric RBDs. A 60-copy particle (noNAG-RBD-E2p) also elicits potently neutralizing antibodies in non-human primates. The neutralizing antibody titers elicited by noNAG-RBD-E2p are comparable to a benchmark stabilized spike antigen and reach levels against Omicron BA.5 that suggest that it would provide protection against emerging variants. SARS-CoV-2 RBD vaccines are cost effective but require methods to increase their potency. Dickey et al. use a computational design method to create a stabilized non-glycosylated RBD that can be fused to a nanoparticle carrier, boosting its potency to levels of a gold-standard spike antigen.
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影响因子：
9.2
作者：
Nguyen B;Tolia NH
通讯作者：
Tolia NH
DOI：
10.3390/v13050893
发表时间：
2021-05-12
期刊：
Viruses
影响因子：
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作者：
Bennett RS;Postnikova EN;Liang J;Gross R;Mazur S;Dixit S;Kocher G;Yu S;Georgia-Clark S;Gerhardt D;Cai Y;Marron L;Lukin VV;Holbrook MR
通讯作者：
Holbrook MR
DOI：
10.1126/science.abq0203
发表时间：
2022-08-19
期刊：
Science (New York, N.Y.)
影响因子：
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通讯作者：
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DOI：
10.1073/pnas.2109744118
发表时间：
2021-12-14
影响因子：
11.1
作者：
Liu X;Luongo C;Matsuoka Y;Park HS;Santos C;Yang L;Moore IN;Afroz S;Johnson RF;Lafont BAP;Martens C;Best SM;Munster VJ;Hollý J;Yewdell JW;Le Nouën C;Munir S;Buchholz UJ
通讯作者：
Buchholz UJ
DOI：
10.1126/science.abm3425
发表时间：
2022-01-07
期刊：
Science (New York, N.Y.)
影响因子：
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