Safety and efficacy of the intranasal spray SARS-CoV-2 vaccine dNS1-RBD: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

作者：Fengcai Zhu, Shoujie Huang, Xiaohui Liu, Qi Chen, Chunlan Zhuang, Hui Zhao, Jinle Han, Anjuli May Jaen, Hung Thai, Jonny Peter, Alexander Gonzalez Dorado, Louie Tirador, Gelza Mae A Zabat, Ralph Elvi Villalobos, Gemalyn Pineda Gueco, Lauren Livia Greta Botha, Shirley Patricia Iglesias Pertuz, Jiaxiang Tan, Kongxin Zhu, Jiali Quan, Hongyan Lin, Yue Huang, Jizong Jia, Xiafei Chu, Junyu Chen, Yixin Chen, Tianying Zhang, Yingying Su, Changgui Li, Xiangzhong Ye, Ting Wu, Jun Zhang, Ningshao Xia · 发表于：The Lancet Respiratory Medicine · 年份：2023 · DOI：10.1016/s2213-2600(23)00349-1 · 被引用次数：72 · 研究领域：SARS-CoV-2 and COVID-19 Research、Advanced Drug Delivery Systems、SARS-CoV-2 detection and testing

BACKGROUND: The live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine (dNS1-RBD, Pneucolin; Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) confers long-lasting and broad protection in animal models and is, to our knowledge, the first COVID-19 mucosal vaccine to enter into human trials, but its efficacy is still unknown. We aimed to assess the safety and efficacy (but not the immunogenicity) of dNS1-RBD against COVID-19. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, adaptive design, phase 3 trial at 33 centres (private or public hospitals, clinical research centres, or Centre for Disease Control and Prevention) in four countries (Colombia, Philippines, South Africa, and Viet Nam). Men and non-pregnant women (aged ≥18 years) were eligible if they had never been infected with SARS-CoV-2, and if they did not have a SARS-CoV-2 vaccination history at screening or if they had received at least one dose of other SARS-CoV-2 vaccines 6 months or longer before enrolment. Eligible adults were randomly assigned (1:1) to receive two intranasal doses of dNS1-RBD or placebo administered 14 days apart (0·2 mL per dose; 0·1 mL per nasal cavity), with block randomisation via an interactive web-response system, stratified by centre, age group (18-59 years or ≥60 years), and SARS-CoV-2 vaccination history. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary outcomes were safety o...