| Autor: |
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, Yunlong Cao, Youchun Wang, Zhuo Zhou, Xiaozhong Peng, Jianwei Wang, Xiaoliang Sunney Xie, Wensheng Wei |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its emerging variants of concern (VOC), such as Delta (B.1.617.2) and Omicron (B.1.1.529), has continued to drive the worldwide pandemic. Therefore, there is a high demand for vaccines with enhanced efficacy, high thermostability, superior design flexibility, and fast manufacturing speed. Here, we report a circular RNA (circRNA) vaccine that encodes the trimeric RBD of SARS-CoV-2 Spike protein. Without the need of nucleotide modification, 5’-capping or 3’-polyadenylation, circRNA could be rapidly produced via in vitro transcription and is highly thermostable whether stored in naked or lipid-nanoparticle (LNP)-encapsulated format. LNP-encapsulated circRNARBD elicited potent neutralizing antibodies and T cell responses, providing robust protection against Beta (B.1.351) and native viruses in mice and rhesus macaques, respectively. Notably, circRNA vaccine enabled higher and more durable antigen production than 1mΨ-modified mRNA vaccine, eliciting a higher proportion of neutralizing antibodies and stronger Th1-biased immune responses. Importantly, we found that circRNARBD-Omicron vaccine induced effective neutralizing antibodies against only Omicron but not Delta variant. By contrast, circRNARBD-Delta could elicit high level of neutralizing antibodies against both Delta and Omicron. Following two doses of either native- or Delta-specific vaccination, circRNARBD-Delta, but not Omicron or Beta vaccines, could effectively boost the neutralizing antibodies against both Delta and Omicron variants. These results suggest that circRNARBD-Delta is a favorable choice for vaccination to provide a broad-spectrum protection against the current variants of concern of SARS-CoV-2. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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