Kim Young-Il, Kim Dokyun, Yu Kwang-Min, Seo Hogyu David, Lee Shin-Ae, Casel Mark Anthony B, Jang Seung-Gyu, Kim Stephanie, Jung WooRam, Lai Chih-Jen, Choi Young Ki, Jung Jae U
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
Zoonotic Infectious Disease Research Center, Chungbuk National University, Cheongju, Republic of Korea.
bioRxiv. 2021 Jan 29:2021.01.28.428743. doi: 10.1101/2021.01.28.428743.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of COVID-19 pandemic, enters host cells the interaction of its Receptor-Binding Domain (RBD) of Spike protein with host Angiotensin-Converting Enzyme 2 (ACE2). Therefore, RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection. In this study, we report the development of RBD protein-based vaccine candidate against SARS-CoV-2 using self-assembling -bullfrog ferritin nanoparticles as an antigen delivery. RBD-ferritin protein purified from mammalian cells efficiently assembled into 24-mer nanoparticles. 16-20 months-old ferrets were vaccinated with RBD-ferritin nanoparticles (RBD-nanoparticles) by intramuscular or intranasal inoculation. All vaccinated ferrets with RBD-nanoparticles produced potent neutralizing antibodies against SARS-CoV-2. Strikingly, vaccinated ferrets demonstrated efficient protection from SARS-CoV-2 challenge, showing no fever, body weight loss and clinical symptoms. Furthermore, vaccinated ferrets showed rapid clearance of infectious viruses in nasal washes and lungs as well as viral RNA in respiratory organs. This study demonstrates the Spike RBD-nanoparticle as an effective protein vaccine candidate against SARS-CoV-2.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是新冠疫情的病原体，它通过其刺突蛋白的受体结合域（RBD）与宿主血管紧张素转换酶2（ACE2）的相互作用进入宿主细胞。因此，RBD是诱导针对SARS-CoV-2感染的保护性免疫的一个有前景的疫苗靶点。在本研究中，我们报告了使用自组装的牛蛙铁蛋白纳米颗粒作为抗原递送载体，开发基于RBD蛋白的抗SARS-CoV-2疫苗候选物。从哺乳动物细胞中纯化的RBD-铁蛋白蛋白有效地组装成24聚体纳米颗粒。对16至20月龄的雪貂通过肌肉注射或鼻内接种RBD-铁蛋白纳米颗粒（RBD-纳米颗粒）进行疫苗接种。所有接种RBD-纳米颗粒的雪貂都产生了针对SARS-CoV-2的强效中和抗体。令人惊讶的是，接种疫苗的雪貂对SARS-CoV-2攻击表现出有效的保护作用，没有出现发烧、体重减轻和临床症状。此外，接种疫苗的雪貂在鼻腔冲洗液和肺部的传染性病毒以及呼吸器官中的病毒RNA清除迅速。这项研究证明了刺突RBD-纳米颗粒是一种有效的抗SARS-CoV-2蛋白疫苗候选物。
