Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19.
Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19.
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DOI：
10.1016/j.ymthe.2021.04.022
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发表时间：
2021-08-04
期刊：
影响因子：
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通讯作者：
Vitelli A
中科院分区：
文献类型：
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作者：
Capone S;Raggioli A;Gentile M;Battella S;Lahm A;Sommella A;Contino AM;Urbanowicz RA;Scala R;Barra F;Leuzzi A;Lilli E;Miselli G;Noto A;Ferraiuolo M;Talotta F;Tsoleridis T;Castilletti C;Matusali G;Colavita F;Lapa D;Meschi S;Capobianchi M;Soriani M;Folgori A;Ball JK;Colloca S;Vitelli A
2019冠状病毒病（COVID-19）大流行由紧急严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起，威胁全球公共卫生，迫切需要开发安全有效的疫苗。在这里，我们报告了一种新的复制缺陷型大猩猩腺病毒载体疫苗的产生和临床前评价，该疫苗编码融合前稳定的SARS-CoV-2 Spike（S）蛋白。我们表明，我们的候选疫苗，GRAd-COV 2，是高度免疫原性的小鼠和猕猴，引发功能性抗体，中和SARS-CoV-2感染和阻断刺突蛋白结合ACE 2受体，和一个强大的，辅助性T细胞（Th）1为主的细胞反应。我们在这里表明，融合前稳定的刺突抗原在诱导ACE 2干扰、SARS-CoV-2中和抗体方面优于野生型，这是上级的。为了面对大规模疫苗生产的前所未有的需求，比较了不同的格拉德基因组缺失，以选择在搅拌罐生物反应器中显示最高生产率的载体骨架。这一初步数据集将GRAd-COV 2确定为潜在的COVID-19候选疫苗，支持GRAd-COV 2疫苗在目前正在进行的I期临床试验中的转化（ClinicalTrials.gov：NCT 04528641）。对抗COVID-19大流行需要安全有效的疫苗。在这里，我们报告了GRAd-COV 2的临床前评价，GRAd-COV 2是一种来自大猩猩的复制缺陷型腺病毒载体，编码融合前稳定的SARS-CoV-2刺突蛋白。GRAd-COV 2目前正在2/3期临床研究中进行测试。
The coronavirus disease 2019 (COVID-19) pandemic caused by the emergent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health, and there is an urgent need to develop safe and effective vaccines. Here, we report the generation and the preclinical evaluation of a novel replication-defective gorilla adenovirus-vectored vaccine encoding the pre-fusion stabilized Spike (S) protein of SARS-CoV-2. We show that our vaccine candidate, GRAd-COV2, is highly immunogenic both in mice and macaques, eliciting both functional antibodies that neutralize SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and a robust, T helper (Th)1-dominated cellular response. We show here that the pre-fusion stabilized Spike antigen is superior to the wild type in inducing ACE2-interfering, SARS-CoV-2-neutralizing antibodies. To face the unprecedented need for vaccine manufacturing at a massive scale, different GRAd genome deletions were compared to select the vector backbone showing the highest productivity in stirred tank bioreactors. This preliminary dataset identified GRAd-COV2 as a potential COVID-19 vaccine candidate, supporting the translation of the GRAd-COV2 vaccine in a currently ongoing phase I clinical trial (ClinicalTrials.gov: NCT04528641). Safe and effective vaccines are needed to fight the COVID-19 pandemic. Here, we report the preclinical evaluation of GRAd-COV2, a replication-defective adenovirus vector derived from a gorilla and encoding the pre-fusion stabilized Spike protein of SARS-CoV-2. GRAd-COV2 is currently being tested in phase 2/3 clinical studies.
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影响因子：
82.9
作者：
Long, Quan-Xin;Liu, Bai-Zhong;Huang, Ai-Long
通讯作者：
Huang, Ai-Long
影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者：
Robertson, Michael N.
DOI：
10.1056/nejmoa2101544
发表时间：
2021-06-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sadoff J;Gray G;Vandebosch A;Cárdenas V;Shukarev G;Grinsztejn B;Goepfert PA;Truyers C;Fennema H;Spiessens B;Offergeld K;Scheper G;Taylor KL;Robb ML;Treanor J;Barouch DH;Stoddard J;Ryser MF;Marovich MA;Neuzil KM;Corey L;Cauwenberghs N;Tanner T;Hardt K;Ruiz-Guiñazú J;Le Gars M;Schuitemaker H;Van Hoof J;Struyf F;Douoguih M;ENSEMBLE Study Group
通讯作者：
ENSEMBLE Study Group
疫苗吸引的人T细胞识别保守的蛋白质区域抑制HIV-1。
DOI：
10.1038/mt.2013.248
发表时间：
2014-02
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
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作者：
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影响因子：
10.7
作者：
Kumar, Sudhir;Stecher, Glen;Tamura, Koichiro
通讯作者：
Tamura, Koichiro