Sun Weina, Leist Sarah R, McCroskery Stephen, Liu Yonghong, Slamanig Stefan, Oliva Justine, Amanat Fatima, Schäfer Alexandra, Dinnon Kenneth H, García-Sastre Adolfo, Krammer Florian, Baric Ralph S, Palese Peter
bioRxiv. 2020 Jul 28:2020.07.26.221861. doi: 10.1101/2020.07.26.221861.
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 or a pre-fusion membrane anchored format. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle mouse study, we report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly. 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 spike (S) protein of the SARS-CoV-2 is the major antigen that notably induces neutralizing antibodies to block viral entry. Many COVID-19 vaccines are under development, among them viral vectors expressing the S protein of SARS-CoV-2 exhibit many benefits. Viral vector vaccines have the potential of being used as both live or inactivated vaccines and they can induce Th1 and Th2-based immune responses following different immunization regimens. Additionally, viral vector vaccines can be handled under BSL-2 conditions and they grow to high titers in cell cultures or other species restricted-hosts. For a SARS-CoV-2 vaccine, several viral vectors are being tested, such as adenovirus, measles virus and Modified vaccinia Ankara. The NDV vector vaccine against SARS-CoV-2 described in this study has advantages similar to those of other viral vector vaccines. But the NDV vector can be amplified in embryonated chicken eggs, which allows for high yields and low costs per dose. Also, the NDV vector is not a human pathogen, therefore the delivery of the foreign antigen would not be compromised by any pre-existing immunity in humans. Finally, NDV has a very good safety record in humans, as it has been used in many oncolytic virus trials. This study provides an important option for a cost-effective SARS-CoV-2 vaccine. This study informs of the value of a viral vector vaccine against SARS-CoV-2. Specifically, for this NDV based SARS-CoV-2 vaccine, the existing egg-based influenza virus vaccine manufactures in the U.S. and worldwide would have the capacity to rapidly produce hundreds of millions of doses to mitigate the consequences of the ongoing COVID-19 pandemic.
由于人类对新出现的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）缺乏保护性免疫，这种病毒已在全球范围内引发大规模疫情，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。在此，我们描述了表达野生型或融合前膜锚定形式的SARS-CoV-2刺突蛋白的新城疫病毒（NDV）载体疫苗。所有描述的NDV载体疫苗在鸡胚中生长至高效价。在一项原理验证小鼠研究中，我们报告称，当肌肉注射疫苗时，NDV载体疫苗可诱导高水平的中和抗体。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，肺部未检测到病毒滴度和病毒抗原。
SARS-CoV-2的刺突（S）蛋白是主要抗原，可显著诱导中和抗体以阻断病毒进入。许多COVID-19疫苗正在研发中，其中表达SARS-CoV-2 S蛋白的病毒载体具有许多优势。病毒载体疫苗有潜力用作活疫苗或灭活疫苗，并且在不同免疫方案后可诱导基于Th1和Th2的免疫反应。此外，病毒载体疫苗可在生物安全二级条件下处理，并且在细胞培养物或其他物种限制宿主中生长至高效价。对于SARS-CoV-2疫苗，正在测试几种病毒载体，如腺病毒、麻疹病毒和改良安卡拉痘苗病毒。本研究中描述的针对SARS-CoV-2的NDV载体疫苗具有与其他病毒载体疫苗类似的优势。但NDV载体可在鸡胚中扩增，这使得每剂产量高且成本低。此外，NDV载体不是人类病原体，因此外源抗原的递送不会受到人类任何预先存在的免疫的影响。最后，NDV在人类中有非常好的安全记录，因为它已用于许多溶瘤病毒试验。本研究为一种具有成本效益的SARS-CoV-2疫苗提供了重要选择。本研究说明了针对SARS-CoV-2的病毒载体疫苗的价值。具体而言，对于这种基于NDV的SARS-CoV-2疫苗，美国和全球现有的基于鸡蛋的流感病毒疫苗生产商有能力迅速生产数亿剂疫苗，以减轻正在进行的COVID-19大流行的后果。
