Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
EBioMedicine. 2020 Dec;62:103132. doi: 10.1016/j.ebiom.2020.103132. Epub 2020 Nov 21.
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.
由于人类对新出现的 SARS-CoV-2 缺乏保护性免疫，这种病毒在全球范围内引发了大规模的大流行，导致数十万人死亡。因此，迫切需要疫苗来控制病毒的传播。
在这里，我们描述了表达 SARS-CoV-2 刺突蛋白的新城疫病毒（NDV）载体疫苗，其形式为野生型或缺乏多碱性切割位点的膜锚定型。所有描述的 NDV 载体疫苗在鸡胚中均能生长到高滴度。在一项原理验证的小鼠研究中，研究了这些基于 NDV 的疫苗的免疫原性和保护效力。
我们报告说，NDV 载体疫苗在小鼠中肌肉内给药时会引发高水平的抗体，这些抗体具有中和作用。重要的是，这些 COVID-19 候选疫苗可保护小鼠免受适应小鼠的 SARS-CoV-2 攻击，而在肺部中未检测到病毒滴度和病毒抗原。
结果表明，表达野生型 S 或不具有多碱性切割位点的膜锚定 S 的 NDV 载体可作为针对 SARS-CoV-2 的活载体疫苗使用。
这项工作得到了美国国立卫生研究院传染病与过敏研究所资助的卓越流感研究与监测中心（CEIRS）合同、合作流感疫苗创新中心（CIVIC）合同、慈善捐款和 NIH 拨款的支持。
