Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection.
Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection.
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DOI：
10.1371/journal.ppat.1009897
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发表时间：
2021-09
期刊：
影响因子：
6.7
通讯作者：
Li F
中科院分区：
文献类型：
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作者：
Geng Q;Tai W;Baxter VK;Shi J;Wan Y;Zhang X;Montgomery SA;Taft-Benz SA;Anderson EJ;Knight AC;Dinnon KH 3rd;Leist SR;Baric RS;Shang J;Hong SW;Drelich A;Tseng CK;Jenkins M;Heise M;Du L;Li F
抗击新冠肺炎大流行及其潜在后果的关键是开发各种有效和安全的疫苗，产生持久免疫，并覆盖一系列SARS-CoV-2变种。重组病毒受体结合域(RBDS)是安全的候选疫苗，但由于缺乏病毒样免疫原展示模式，其效果往往有限。在这里，我们开发了一种新型的病毒样纳米颗粒(VLP)疫苗，它的表面显示了120个副本的SARS-CoV-2 RBD。这种VLP-RBD疫苗在免疫原展示中模仿了基于病毒的疫苗，这提高了其效力，同时保持了基于蛋白质的亚单位疫苗的安全性。与RBD疫苗相比，VLP-RBD疫苗在小鼠体内诱导的中和抗体增加了5倍，有效地阻止了SARS-CoV-2与宿主受体的结合，并有效地中和了SARS-CoV-2变异株、SARS-CoV-1和SARS-CoV-1相关蝙蝠冠状病毒的细胞侵入。在两个月的研究期间，VLP-RBD疫苗诱导的这些中和免疫反应并没有减弱。此外，VLP-RBD疫苗有效地保护小鼠免受SARS-CoV-2攻击，显著减少了免疫小鼠的临床症状和病理变化。VLP-RBD疫苗为控制SARS-CoV-2的传播提供了一种潜在的有效解决方案。目前正在分发基于信使核糖核酸和病毒载体的疫苗，以遏制新冠肺炎大流行。继续开发更多种类的SARS-CoV-2疫苗将有助于对抗SARS-CoV-2的许多变种。在这里，我们开发了一种病毒样颗粒(VLP)疫苗，它结合了基于病毒的疫苗的有效性和基于蛋白质的疫苗的安全性。该疫苗以鲁马津合成酶纳米颗粒蛋白为结构支架，以120个拷贝的SARS-CoV-2受体结合域为表面免疫原，在小鼠体内诱导了持续2个月的高滴度中和抗体应答，并对SARS-CoV-2、SARS-CoV-1及其变种有较强的抑制作用。VLP疫苗还保护小鼠免受高滴度SARS-CoV-2的攻击。新型VLP疫苗可能有助于保护人类免受SARS-CoV-2及其变种的影响。
The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) are safe vaccine candidates but often have limited efficacy due to the lack of virus-like immunogen display pattern. Here we have developed a novel virus-like nanoparticle (VLP) vaccine that displays 120 copies of SARS-CoV-2 RBD on its surface. This VLP-RBD vaccine mimics virus-based vaccines in immunogen display, which boosts its efficacy, while maintaining the safety of protein-based subunit vaccines. Compared to the RBD vaccine, the VLP-RBD vaccine induced five times more neutralizing antibodies in mice that efficiently blocked SARS-CoV-2 from attaching to its host receptor and potently neutralized the cell entry of variant SARS-CoV-2 strains, SARS-CoV-1, and SARS-CoV-1-related bat coronavirus. These neutralizing immune responses induced by the VLP-RBD vaccine did not wane during the two-month study period. Furthermore, the VLP-RBD vaccine effectively protected mice from SARS-CoV-2 challenge, dramatically reducing the development of clinical signs and pathological changes in immunized mice. The VLP-RBD vaccine provides one potentially effective solution to controlling the spread of SARS-CoV-2. Both mRNA-based and viral vector-based vaccines are currently being distributed to curtail the COVID-19 pandemic. Continued development of more varieties of SARS-CoV-2 vaccines will help battle the many variants of SARS-CoV-2. Here we have developed a virus-like particle (VLP) vaccine that combines the effectiveness of virus-based vaccines and safety of protein-based vaccines. Using the lumazine synthase nanoparticle protein as the structural scaffold and 120 copies of SARS-CoV-2 receptor-binding domain as the surface immunogen, this VLP vaccine induced high-titer neutralizing antibody responses in mice that lasted >2 months and potently inhibited SARS-CoV-2, SARS-CoV-1, and their variants. The VLP vaccine also protected mice from high-titer SARS-CoV-2 challenge. The novel VLP vaccine may contribute to the protection of the human population from SARS-CoV-2 and its variants.
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DOI：
10.1038/nrmicro2147
发表时间：
2009-06
期刊：
Nature reviews. Microbiology
影响因子：
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作者：
通讯作者：
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影响因子：
5.8
作者：
Du L;Yang Y;Zhou Y;Lu L;Li F;Jiang S
通讯作者：
Jiang S
影响因子：
16.6
作者：
Du, Lanying;Tai, Wanbo;Yang, Yang;Zhao, Guangyu;Zhu, Qing;Sun, Shihui;Liu, Chang;Tao, Xinrong;Tseng, Chien-Te K.;Perlman, Stanley;Jiang, Shibo;Zhou, Yusen;Li, Fang
通讯作者：
Li, Fang
影响因子：
5.5
作者：
Ma, Cuiqing;Wang, Lili;Tao, Xinrong;Zhang, Naru;Yang, Yang;Tseng, Chien-Te K.;Li, Fang;Zhou, Yusen;Jiang, Shibo;Du, Lanying
通讯作者：
Du, Lanying
DOI：
10.1038/nrmicro2090
发表时间：
2009-03
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
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