A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses.
A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses.
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DOI：
10.1038/s41467-020-20654-7
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发表时间：
2021-01-22
影响因子：
16.6
通讯作者：
Townsend AR
中科院分区：
文献类型：
--
作者：
Tan TK;Rijal P;Rahikainen R;Keeble AH;Schimanski L;Hussain S;Harvey R;Hayes JWP;Edwards JC;McLean RK;Martini V;Pedrera M;Thakur N;Conceicao C;Dietrich I;Shelton H;Ludi A;Wilsden G;Browning C;Zagrajek AK;Bialy D;Bhat S;Stevenson-Leggett P;Hollinghurst P;Tully M;Moffat K;Chiu C;Waters R;Gray A;Azhar M;Mioulet V;Newman J;Asfor AS;Burman A;Crossley S;Hammond JA;Tchilian E;Charleston B;Bailey D;Tuthill TJ;Graham SP;Duyvesteyn HME;Malinauskas T;Huo J;Tree JA;Buttigieg KR;Owens RJ;Carroll MW;Daniels RS;McCauley JW;Stuart DI;Huang KA;Howarth M;Townsend AR
需要有效和负担得起的SARS-CoV-2疫苗来应对正在发生的大流行。在这项研究中，我们描述了一种针对SARS-CoV-2的蛋白质纳米颗粒疫苗。该疫苗基于使用SpyTag/SpyCatcher技术在合成病毒样颗粒（VLP）平台SpyCatcher 003-mi 3上展示冠状病毒刺突糖蛋白受体结合结构域（RBD）。在初免-加强方案中低剂量的RBD-SpyVLP在小鼠和猪中诱导强中和抗体应答，其上级恢复期人血清。我们使用ACE 2阻断和中和假病毒或野生型SARS-CoV-2的细胞感染来评估抗体质量。使用单克隆抗体面板的竞争测定，我们表明，RBD-SpyVLP诱导多克隆抗体反应，识别RBD上的关键表位，减少选择中和逃逸突变体的可能性。此外，RBD-SpyVLP是热稳定的，可以冻干而不失去免疫原性，以促进全球分布和减少冷链依赖。数据表明，RBD-SpyVLP为应对COVID-19大流行的临床和物流挑战提供了强大的潜力。SARS-COV-2疫苗在持续的大流行中是必要的。在这里，作者描述了一种候选疫苗，该疫苗使用SpyTag/SpyCatcher技术在合成VLP平台上呈现SARS-CoV-2刺突蛋白的受体结合结构域（RBD），并显示了小鼠和猪的初免-加强方案的免疫原性。
There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic. Vaccines for SARS-COV-2 are needed in the ongoing pandemic. Here the authors characterize a vaccine candidate that presents the receptor-binding domain (RBD) of SARS-CoV-2 spike protein on a synthetic VLP platform using SpyTag/SpyCatcher technology and show immunogenicity of a prime-boost regimen in mice and pigs.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
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：
28.3
作者：
Gorbalenya, Alexander E.;Baker, Susan C.;Ziebuhr, John
通讯作者：
Ziebuhr, John
影响因子：
16.8
作者：
Huo, Jiangdong;Le Bas, Audrey;Naismith, James H.
通讯作者：
Naismith, James H.
影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F