The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice.
The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice.
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DOI：
10.1038/s41392-021-00750-w
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发表时间：
2021-09-09
影响因子：
39.3
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Sun W;He L;Zhang H;Tian X;Bai Z;Sun L;Yang L;Jia X;Bi Y;Luo T;Cheng G;Fan W;Liu W;Li J
随着新冠肺炎在全球范围内继续快速传播，变异株不断涌现，迫切需要开发和部署安全有效的疫苗。在这里，我们开发了一种基于SARS-CoV-2尖峰蛋白(S)的三聚体受体结合结构域(RbD)与铁蛋白形成的纳米颗粒(Tf-RBD)融合的基因疫苗。与RBD基因疫苗的三聚体形式(T-RBD)相比，TF-RBD可在肌肉内诱导出强大而持久的体液免疫以及偏向Th1的细胞反应。在用SARS-CoV-2活病毒进一步攻击后，两次低剂量的Tf-RBD免疫方案对转导hACE2的小鼠提供了足够的保护。此外，Tf-RBD的mRNA模板被轻松、快速地设计成一种变异疫苗，以应对SARS-CoV-2突变。TF-RBD多价疫苗产生了针对Alpha(B.1.1.7)和Beta(B.1.351)变种的广谱中和抗体。这种基于编码的自组装纳米颗粒三聚体RBD的mRNA疫苗为设计针对SARS-CoV-2的mRNA疫苗提供了参考。
As COVID-19 continues to spread rapidly worldwide and variants continue to emerge, the development and deployment of safe and effective vaccines are urgently needed. Here, we developed an mRNA vaccine based on the trimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein fused to ferritin-formed nanoparticles (TF-RBD). Compared to the trimeric form of the RBD mRNA vaccine (T-RBD), TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th1-biased cellular response. After further challenge with live SARS-CoV-2, immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice. In addition, the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations. The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha (B.1.1.7) and Beta (B.1.351) variants. This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a reference for the design of mRNA vaccines targeting SARS-CoV-2.
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影响因子：
16.6
作者：
Huang QS;Wood T;Jelley L;Jennings T;Jefferies S;Daniells K;Nesdale A;Dowell T;Turner N;Campbell-Stokes P;Balm M;Dobinson HC;Grant CC;James S;Aminisani N;Ralston J;Gunn W;Bocacao J;Danielewicz J;Moncrieff T;McNeill A;Lopez L;Waite B;Kiedrzynski T;Schrader H;Gray R;Cook K;Currin D;Engelbrecht C;Tapurau W;Emmerton L;Martin M;Baker MG;Taylor S;Trenholme A;Wong C;Lawrence S;McArthur C;Stanley A;Roberts S;Rahnama F;Bennett J;Mansell C;Dilcher M;Werno A;Grant J;van der Linden A;Youngblood B;Thomas PG;NPIsImpactOnFlu Consortium;Webby RJ
通讯作者：
Webby RJ
DOI：
10.1016/s2468-2667(21)00055-4
发表时间：
2021-05
期刊：
The Lancet. Public health
影响因子：
--
作者：
Graham MS;Sudre CH;May A;Antonelli M;Murray B;Varsavsky T;Kläser K;Canas LS;Molteni E;Modat M;Drew DA;Nguyen LH;Polidori L;Selvachandran S;Hu C;Capdevila J;COVID-19 Genomics UK (COG-UK) Consortium;Hammers A;Chan AT;Wolf J;Spector TD;Steves CJ;Ourselin S
通讯作者：
Ourselin S
影响因子：
5.4
作者：
Chen, Wen-Hsiang;Strych, Ulrich;Bottazzi, Maria Elena
通讯作者：
Bottazzi, Maria Elena
DOI：
10.1016/j.bbrc.2020.10.102
发表时间：
2021-01-29
影响因子：
3.1
作者：
Giovanetti M;Benedetti F;Campisi G;Ciccozzi A;Fabris S;Ceccarelli G;Tambone V;Caruso A;Angeletti S;Zella D;Ciccozzi M
通讯作者：
Ciccozzi M
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group