Baiya Phytopharm Co., Ltd, Bangkok 10330, Thailand.
Center of Excellence in Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok 10330, Thailand; Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Vaccine. 2022 Jul 30;40(32):4440-4452. doi: 10.1016/j.vaccine.2022.05.087. Epub 2022 Jun 6.
Coronavirus disease 2019 (COVID-19) is an acute respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The prevention of SARS-CoV-2 transmission has become a global priority. Previously, we showed that a protein subunit vaccine that was developed based on the fusion of the SARS-CoV-2 receptor-binding domain (RBD) to the Fc portion of human IgG1 (RBD-Fc), produced in Nicotiana benthamiana, and adjuvanted with alum, namely, Baiya SARS-CoV-2 Vax 1, induced potent immunological responses in both mice and cynomolgus monkeys. Hence, this study evaluated the protective efficacy, safety, and toxicity of Baiya SARS-CoV-2 Vax 1 in K18-hACE2 mice, monkeys and Wistar rats. Two doses of vaccine were administered three weeks apart on Days 0 and 21. The administration of the vaccine to K18-hACE2 mice reduced viral loads in the lungs and brains of the vaccinated animals and protected the mice against challenge with SARS-CoV-2. In monkeys, the results of safety pharmacology tests, general clinical observations, and a core battery of studies of three vital systems, namely, the central nervous, cardiovascular, and respiratory systems, did not reveal any safety concerns. The toxicology study of the vaccine in rats showed no vaccine-related pathological changes, and all the animals remained healthy under the conditions of this study. Furthermore, the vaccine did not cause any abnormal toxicity in rats and was clinically tolerated even at the highest tested concentration. In addition, general health status, body temperature, local toxicity at the administration site, hematology, and blood chemistry parameters were also monitored. Overall, this work presents the results of the first systematic study of the safety profile of a plant-derived vaccine, Baiya SARS-CoV-2 Vax 1; this approach can be considered a viable strategy for the development of vaccines against COVID-19.
新型冠状病毒病（COVID-19）是由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的急性呼吸道疾病。预防 SARS-CoV-2 传播已成为全球首要任务。此前，我们表明，一种基于 SARS-CoV-2 受体结合域（RBD）与人 IgG1 的 Fc 部分融合的蛋白亚单位疫苗（RBD-Fc），在黄花烟中生产，并与明矾佐剂一起使用，即百亚 SARS-CoV-2 Vax 1，在小鼠和食蟹猴中均诱导出强烈的免疫反应。因此，本研究评估了百亚 SARS-CoV-2 Vax 1 在 K18-hACE2 小鼠、猴子和 Wistar 大鼠中的保护效力、安全性和毒性。疫苗在第 0 天和第 21 天间隔三周给予两次剂量。疫苗接种可降低 K18-hACE2 小鼠肺部和脑部的病毒载量，并保护小鼠免受 SARS-CoV-2 的攻击。在猴子中，安全药理学测试、一般临床观察以及三个重要系统（中枢神经系统、心血管系统和呼吸系统）的核心电池研究结果均未显示出任何安全性问题。疫苗在大鼠中的毒理学研究表明，没有与疫苗相关的病理变化，在本研究条件下，所有动物均保持健康。此外，疫苗在大鼠中不会引起任何异常毒性，即使在测试的最高浓度下也具有临床耐受性。此外，还监测了一般健康状况、体温、给药部位局部毒性、血液学和血液化学参数。总之，这项工作介绍了植物源疫苗百亚 SARS-CoV-2 Vax 1 安全性特征的首次系统性研究结果；这种方法可以被认为是开发 COVID-19 疫苗的可行策略。
