Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models.
Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models.
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表达预灌注稳定的SARS-COV-2峰值糖蛋白的离发病毒菌株MVA可诱导强大的保护并防止小鼠和仓鼠模型中的脑感染。
DOI：
10.3390/vaccines11051006
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发表时间：
2023-05-21
期刊：
影响因子：
7.8
通讯作者：
Blasco R
中科院分区：
文献类型：
--
作者：
Lorenzo MM;Marín-López A;Chiem K;Jimenez-Cabello L;Ullah I;Utrilla-Trigo S;Calvo-Pinilla E;Lorenzo G;Moreno S;Ye C;Park JG;Matía A;Brun A;Sánchez-Puig JM;Nogales A;Mothes W;Uchil PD;Kumar P;Ortego J;Fikrig E;Martinez-Sobrido L;Blasco R
COVID-19疫情凸显了迅速应对的重要性以及疫苗开发可靠技术的必要性。我们的团队以前开发了一个快速克隆系统，用于改良的安卡拉牛痘病毒（MVA）疫苗平台。在这项研究中，我们报告了使用该系统获得的重组MVA疫苗的构建和临床前测试。我们获得了表达含有D 614 G氨基酸取代的未修饰的全长SARS-CoV-2刺突（S）蛋白的重组MVA（MVA-Sdg）和表达含有氨基酸取代的修饰的S蛋白的版本（MVA-Spf），所述氨基酸取代被设计成使蛋白a稳定在融合前构象。发现MVA-Sdg表达的S蛋白被表达，并被正确加工和转运到细胞表面，在那里它有效地产生细胞-细胞融合。然而，Spf型没有经过蛋白水解处理，尽管被转运到质膜，但它未能诱导细胞-细胞融合。我们在易感转基因K18-人血管紧张素转换酶2（K18-hACE 2）小鼠和金黄色叙利亚仓鼠中评估了两种疫苗候选物的初免-加强方案。在两种动物模型中，任一疫苗均诱导了强大的免疫力和疾病保护。值得注意的是，MVA-Spf候选疫苗产生了更高水平的抗体，更强的T细胞反应和更高程度的保护。此外，SARS-CoV-2在MVA-Spf接种小鼠脑中的水平降低至检测不到的水平。这些结果增加了我们目前的经验和疫苗载体和技术的范围，以开发安全有效的COVID-19疫苗。
The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we reported on the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino-acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino-acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and was correctly processed and transported to the cell surface, where it efficiently produced cell–cell fusion. Version Spf, however, was not proteolytically processed, and despite being transported to the plasma membrane, it failed to induce cell–cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin-converting enzyme 2 (K18-hACE2) in mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the level of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine.
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影响因子：
7.7
作者：
Cheetham NJ;Kibble M;Wong A;Silverwood RJ;Knuppel A;Williams DM;Hamilton OKL;Lee PH;Bridger Staatz C;Di Gessa G;Zhu J;Katikireddi SV;Ploubidis GB;Thompson EJ;Bowyer RCE;Zhang X;Abbasian G;Garcia MP;Hart D;Seow J;Graham C;Kouphou N;Acors S;Malim MH;Mitchell RE;Northstone K;Major-Smith D;Matthews S;Breeze T;Crawford M;Molloy L;Kwong ASF;Doores K;Chaturvedi N;Duncan EL;Timpson NJ;Steves CJ
通讯作者：
Steves CJ
DOI：
10.3390/v6072735
发表时间：
2014-07-17
期刊：
Viruses
影响因子：
--
作者：
Altenburg AF;Kreijtz JH;de Vries RD;Song F;Fux R;Rimmelzwaan GF;Sutter G;Volz A
通讯作者：
Volz A
影响因子：
8.8
作者：
Dangi T;Class J;Palacio N;Richner JM;Penaloza MacMaster P
通讯作者：
Penaloza MacMaster P
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
影响因子：
5.5
作者：
Alharbi NK;Padron-Regalado E;Thompson CP;Kupke A;Wells D;Sloan MA;Grehan K;Temperton N;Lambe T;Warimwe G;Becker S;Hill AVS;Gilbert SC
通讯作者：
Gilbert SC