Jia Qingmei, Bielefeldt-Ohmann Helle, Maison Rachel M, Masleša-Galić Saša, Cooper Sarah K, Bowen Richard A, Horwitz Marcus A
Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California - Los Angeles, Los Angeles, CA, USA.
School of Veterinary Science, University of Queensland, Brisbane, QLD, Australia.
NPJ Vaccines. 2021 Mar 30;6(1):47. doi: 10.1038/s41541-021-00321-8.
To generate an inexpensive readily manufactured COVID-19 vaccine, we employed the LVS ΔcapB vector platform, previously used to generate potent candidate vaccines against Select Agent diseases tularemia, anthrax, plague, and melioidosis. Vaccines expressing SARS-CoV-2 structural proteins are constructed using the LVS ΔcapB vector, a highly attenuated replicating intracellular bacterium, and evaluated for efficacy in golden Syrian hamsters, which develop severe COVID-19-like disease. Hamsters immunized intradermally or intranasally with a vaccine co-expressing the Membrane and Nucleocapsid proteins and challenged 5 weeks later with a high dose of SARS-CoV-2 are protected against severe weight loss and lung pathology and show reduced viral loads in the oropharynx and lungs. Protection correlates with anti-Nucleocapsid antibody. This potent vaccine should be safe; inexpensive; easily manufactured, stored, and distributed; and given the high homology between Membrane and Nucleocapsid proteins of SARS-CoV and SARS-CoV-2, potentially serve as a universal vaccine against the SARS subset of pandemic causing β-coronaviruses.
为了研发一种价格低廉、易于生产的新冠疫苗，我们采用了LVS ΔcapB载体平台，该平台此前用于研发针对特定病原体疾病（兔热病、炭疽、鼠疫和类鼻疽）的有效候选疫苗。使用LVS ΔcapB载体构建表达新冠病毒结构蛋白的疫苗，LVS ΔcapB是一种高度减毒的细胞内复制细菌，并在叙利亚金黄地鼠中评估其有效性，这些地鼠会患上严重的类似新冠的疾病。用共表达膜蛋白和核衣壳蛋白（N蛋白）的疫苗皮内或鼻内免疫地鼠，5周后用高剂量新冠病毒攻击，结果显示地鼠可免受严重体重减轻和肺部病变影响，且口咽和肺部的病毒载量降低。保护作用与抗核衣壳抗体相关。这种高效疫苗应具有安全性；价格低廉；易于生产、储存和分发；并且鉴于新冠病毒和新冠病毒-2的膜蛋白和核衣壳蛋白之间高度同源，有可能作为一种针对引起大流行的β冠状病毒中新冠病毒亚群的通用疫苗。
