Newcastle disease virus (NDV) expressing the spike protein of SARS-CoV-2 as a live virus vaccine candidate.
Newcastle disease virus (NDV) expressing the spike protein of SARS-CoV-2 as a live virus vaccine candidate.
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纽卡斯尔病毒（NDV）表达SARS-COV-2的尖峰蛋白作为活病毒疫苗候选者。
DOI：
10.1016/j.ebiom.2020.103132
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发表时间：
2020-12
期刊：
影响因子：
11.1
通讯作者：
Palese P
中科院分区：
文献类型：
--
作者：
Sun W;Leist SR;McCroskery S;Liu Y;Slamanig S;Oliva J;Amanat F;Schäfer A;Dinnon KH 3rd;García-Sastre A;Krammer F;Baric RS;Palese P
由于人类对新出现的SARS-CoV-2缺乏保护性免疫力，该病毒已在全球范围内引发大规模流行，导致数十万人死亡。因此，迫切需要一种疫苗来遏制病毒的传播。在这里，我们描述了新城疫病毒(NDV)载体疫苗以野生型形式或缺乏多碱基切割位点的膜锚定形式表达SARS-CoV-2刺突蛋白。所有描述的新城疫病毒载体疫苗都能在胚胎鸡蛋中生长到高滴度。在一项原理上的小鼠研究中，研究了这些基于新城疫病毒的疫苗的免疫原性和保护效力。我们报告说，新城疫病毒载体疫苗在小鼠肌肉注射疫苗时，会诱导高水平的抗体，这些抗体是中和的。重要的是，这些新冠肺炎候选疫苗保护小鼠免受小鼠适应的SARS-CoV-2挑战，肺部没有检测到病毒滴度和病毒抗原。结果表明，表达野生型S或无多碱基切割位点的膜锚定S的新城疫病毒载体可作为SARS-CoV-2的活载体疫苗。这项工作得到了NIAID资助的流感研究和监测英才中心(CEIRS)合同、合作流感疫苗创新中心(CIRIC)合同、慈善捐款和NIH赠款的支持。
Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type format or a membrane-anchored format lacking the polybasic cleavage site. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle mouse study, the immunogenicity and protective efficacy of these NDV-based vaccines were investigated. We report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly in mice. Importantly, these COVID-19 vaccine candidates protect mice from a mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs. The results suggested that the NDV vector expressing either the wild type S or membrane-anchored S without the polybasic cleavage site could be used as live vector vaccine against SARS-CoV-2. This work is supported by an NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS) contract, the Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract, philanthropic donations and NIH grants.
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影响因子：
11.1
作者：
Vijayakumar, Gayathri;Palese, Peter;Goff, Peter H.
通讯作者：
Goff, Peter 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
影响因子：
3.8
作者：
Römer-Oberdörfer, A;Mundt, E;Mettenleiter, TC
通讯作者：
Mettenleiter, TC
影响因子：
15.8
作者：
ter Meulen, Jan;van den Brink, Edward N.;Poon, Leo L. M.;Marissen, Wilfred E.;Leung, Cynthia S. W.;Cox, Freek;Cheung, Chung Y.;Bakker, Arjen Q.;Bogaards, Johannes A.;van Deventer, Els;Preiser, Wolfgang;Doerr, Hans Wilhelm;Chow, Vincent T.;de Kruif, John;Peiris, Joseph S. M.;Goudsmit, Jaap
通讯作者：
Goudsmit, Jaap
影响因子：
4.7
作者：
Schirrmacher V
通讯作者：
Schirrmacher V