Circular RNA vaccines against SARS-CoV-2 and emerging variants

• DOI: 10.1016/j.cell.2022.03.044
• Publication Date: 2022-04-01T06:07:27Z
• Authors: Liang Qu; Zongyi Yi; Yong Shen; Liangru Lin; Feng Chen; Yiyuan Xu; Zeguang Wu; Huixian Tang; Xiaoxue Zhang; Feng Tian; Chunhui Wang; Xia Xiao; Xiaojing Dong; Li Guo; Shuaiyao Lu; Chengyun Yang; Cong Tang; Yun Yang; Wenhai Yu; Junbin Wang; Yanan Zhou; Qing Huang; Ayijiang Yisimayi; Shuo Liu; Weijin Huang; Yunlong Cao; Youchun Wang; Zhuo Zhou; Xiaozhong Peng; Jianwei Wang; Xiaoliang Sunney Xie; Wensheng Wei
• Keywords: 0301 basic medicine; Vaccines, Synthetic; COVID-19 Vaccines; SARS-CoV-2; COVID-19; RNA, Circular; Antibodies, Viral; Antibodies, Neutralizing; Macaca mulatta; Article; 3. Good health; Mice; 03 medical and health sciences; Animals; Humans; mRNA Vaccines

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.