Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle.
Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle.
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DOI：
10.3390/vaccines9111347
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发表时间：
2021-11-17
期刊：
影响因子：
7.8
通讯作者：
Pogue GP
中科院分区：
文献类型：
--
作者：
Royal JM;Simpson CA;McCormick AA;Phillips A;Hume S;Morton J;Shepherd J;Oh Y;Swope K;DeBeauchamp JL;Webby RJ;Cross RW;Borisevich V;Geisbert TW;Demarco JK;Bratcher B;Haydon H;Pogue GP
稳定、有效、易于生产的疫苗对于阻止由冠状病毒SARS-CoV-2引起的COVID-19大流行至关重要。我们构建了一种候选疫苗CoV-RBD 121-NP，它由SARS-CoV-2受体结合结构域（RBD）的刺突糖蛋白（S）融合到人IgG 1 Fc结构域（CoV-RBD 121），并结合到修饰的烟草花叶病毒（TMV）纳米颗粒。在体外，CoV-RBD 121与宿主病毒受体ACE 2和单克隆抗体CR 3022结合，CR 3022是一种阻断S与ACE 2结合的中和抗体。CoV-RBD 121-NP候选疫苗保留了关键的SARS-CoV-2刺突蛋白表位，具有一致的安全性、同一性和强度的生产放行特性，并在2-8 °C或22- 2 - 8 °C下储存12个月时显示出稳定的效力。免疫原性研究显示，在C57 BL/6小鼠中，无佐剂或佐剂（7909 CpG）制剂产生了强烈的抗体应答。无佐剂疫苗诱导平衡的Th 1/Th 2反应和识别SARS 2-CoV-2的S1结构域和完整S蛋白的抗体，而有佐剂疫苗诱导Th 1偏向反应。如通过三种不同的测定所测量的，含佐剂和无佐剂的疫苗均诱导病毒中和滴度。总的来说，这些数据显示了通过SARS-CoV-2 RBD与TMV样纳米颗粒的结合产生了稳定的COVID-19候选疫苗。
Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2–8 °C or 22–28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle.
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影响因子：
17.1
作者：
Bruun TUJ;Andersson AC;Draper SJ;Howarth M
通讯作者：
Howarth M
影响因子：
9
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Channappanavar R;Perlman S
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Perlman S
影响因子：
5.4
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Peiris, J. S. Malik
影响因子：
3.7
作者：
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Jiang, Shibo
影响因子：
5.5
作者：
Kam YW;Kien F;Roberts A;Cheung YC;Lamirande EW;Vogel L;Chu SL;Tse J;Guarner J;Zaki SR;Subbarao K;Peiris M;Nal B;Altmeyer R
通讯作者：
Altmeyer R