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On March 31, 2022, Wei Wensheng's group from Peking University School of Life Sciences published a research paper titled " Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants " online in the journal Cell , reporting for the first time a circular RNA vaccine technology platform , and the circular RNA vaccine developed against the new coronavirus and its series of variants .
Figure 1 Schematic diagram of the development of 2019-nCoV circRNA vaccine
As a breakthrough medical technology emerging in recent years, the basic principle of mRNA vaccine is to express antigen protein by introducing mRNA into the body through lipid nanoparticles (LNP) to stimulate the body to produce a specific immune response
Wei Wensheng's team first established a technical platform for the efficient preparation of high-purity circular RNA in vitro, and designed a circular RNA vaccine encoding the new coronavirus spike protein (Spike) receptor domain (RBD) for the new coronavirus and its variants
Figure 2 CircRNA vaccination provides significant protection in mice and rhesus monkeys
A series of comparative evaluations showed that compared with mRNA vaccines, circRNA vaccines have the following characteristics or advantages (Figure 3): 1) circRNAs have higher stability and can generate higher levels and more durable antigens in vivo; 2) The proportion of neutralizing antibodies induced by circRNA vaccine is higher, which can more effectively fight against virus mutation and reduce the potential side effects of antibody-dependent enhancement (ADE) of vaccine; 3) The ratio of IgG2/IgG1 induced by circRNA vaccine is higher, indicating that It mainly induces a Th1-type protective T cell immune response, which can effectively reduce the potential side effects of vaccine-associated respiratory diseases (VAERD, Vaccine-associated enhanced respiratory diseases)
Figure 3 Features and advantages of circRNA vaccines (compared to mRNA vaccines)
In addition, after the new coronavirus Omicron mutant was listed as a Variants of Concern (VOC) by the World Health Organization, the research team urgently launched the development of a circular RNA vaccine for the mutant
Figure 4 The circRNA RBD-Delta vaccine designed for the new coronavirus delta variant is a candidate vaccine with broad-spectrum protection
The above results show that the circRNA RBD-Delta vaccine designed for the new coronavirus delta variant is a candidate vaccine for new coronavirus pneumonia with broad-spectrum protection.
Quan Liang, a postdoctoral fellow in Wei Wensheng's research group at Peking University, and Yi Zongyi and Shen Yong, a doctoral student, are the co-first authors of the paper