On June 1, 2023, the Key Laboratory of Molecular Virology and Immunology of the Chinese Academy of Sciences, the Changchun Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, the Key Laboratory of Synthetic Biology of the Chinese Academy of Sciences of the Center of Excellence for Molecular Plants, the National Engineering Technology Research Center for Emergency Prevention and Control Drugs, Changchun University of Chinese Medicine, East China University of Science and Technology, Lingang Laboratory and other multi-unit teams published a report entitled "Multi-valent mRNA vaccines" in SCIENCE CHINA Life Sciences against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity". 

On June 1, 2023, the Key Laboratory of Molecular Virology and Immunology of the Chinese Academy of Sciences, the Changchun Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, the Key Laboratory of Synthetic Biology of the Chinese Academy of Sciences of the Center of Excellence for Molecular Plants, the National Engineering Technology Research Center for Emergency Prevention and Control Drugs, Changchun University of Chinese Medicine, East China University of Science and Technology, Lingang Laboratory and other multi-unit teams published a report entitled "Multi-valent mRNA vaccines" in SCIENCE CHINA Life Sciences against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity". 

On June 1, 2023, the Key Laboratory of Molecular Virology and Immunology of the Chinese Academy of Sciences, the Changchun Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, the Key Laboratory of Synthetic Biology of the Chinese Academy of Sciences of the Center of Excellence for Molecular Plants, the National Engineering Technology Research Center for Emergency Prevention and Control Drugs, Changchun University of Chinese Medicine, East China University of Science and Technology, Lingang Laboratory and other multi-unit teams published a report entitled "Multi-valent mRNA vaccines" in SCIENCE CHINA Life Sciences against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity". 

Monkeypox virus (MPV) belongs to a large family of double-stranded DNA viruses, the orthopoxviridae, which also includes chickenpox virus, smallpox virus, vaccinia virus (VACV) and other viruses. Viruses produce two different forms of viral particles during their replication cycle: enveloped virus (EV) and mature virus (MV). Based on the population immunity study of other orthopoxvirus and the simulation calculation of monkeypox virus surface protein, the researchers selected EV and MV-specific surface antigens, and designed and prepared multivalent mRNA vaccines with different combinations of EV-antigen, MV-antigen, and EV plus MV mixed antigen to study the efficacy and safety of various multivalent mRNA vaccines.

It was found that various surface antigens can strongly induce specific IgG immune responses after vaccination with multivalent mRNA vaccines prepared by different combinations of antigens, but various antigens have different kinetics and reaction intensities. At the same time, the virus neutralization activity of the serum of mice immunized with different antigen combinations correlated well with their total IgG antibody levels. The study also found that the immune response produced by monkeypox virus mRNA vaccinated mRNA mMouse was by inducing an antigen-specific CD4+ T lymphocyte response, which was dependent on Th1 cells.

The VACV challenge experiment of immunized mice found that after immunizing mice with lethal doses of VACV virus infection, four different mRNA multivalent vaccines could protect mice from virus infection and death. Its protective ability was positively correlated with the total IgG response of mice. Hexavalent mRNA vaccines using a combination of two types of viral particles (EV+MV) antigens provide the best protection. In contrast, mice in the control group (placebo shot) were unprotected (sacrificed on day 6 of the Code of Ethics due to severe weight loss).

The above results show that the different immunogenicity and immune neutralization capabilities of the two types of particle surface antigens of monkeypox virus were found by computational analysis of the selected EV/MV virus particle surface antigen combination mRNA vaccine experiment, and the enhanced defense mechanism of multivalent mRNA vaccine against monkeypox virus was revealed. The study provides a mechanistic and kinetic analysis of different monkeypox virus surface antigens and their induced immune responses in vivo. A model of attacking mice with lethal doses of VACV verified the effectiveness of the multivalent mRNA vaccine on the protection of immune mice. The multivalent mRNA vaccine in this study had no toxicity observed in immunized mice and had a good safety profile. This lays the foundation for the further development of highly effective and safe mRNA vaccines to enhance resilience to monkeypox virus epidemic outbreaks.

Niubing Zhang and Xiang Cheng, Key Laboratory of Synthetic Biology, Chinese Academy of Sciences, Zhu Yilong, Chun Veterinary Research Institute, President of Chinese Agricultural Sciences, and Mo Ouyang, Key Laboratory of Molecular Virus and Immunology, Chinese Academy of Sciences, are co-first authors of the paper. Professor Hao Pei of the Key Laboratory of Molecular Virology and Immunology of the Chinese Academy of Sciences, researcher Li Xiao of the Chun Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, researcher Li Xuan of the Key Laboratory of Synthetic Biology of the Chinese Academy of Sciences of the Center of Excellence of Molecular Plants, and researcher Zhong Wu of the National SH Emergency Prevention and Control Drug Engineering Technology Research Center are the co-corresponding authors of the paper. This work was supported by the National Major Special Projects and Key R&D Programs (2021YFC2300704, 2021YFA1301402, 2018YFA0903700), the Strategic Pilot Project of the Chinese Academy of Sciences (XDA24010400), the Shanghai Key Science and Technology Project (ZD2021CY001), and the National Natural Science Foundation of China (32270695, 31972881).

Original link:

https://engine.scichina.com/doi/10.1007/s11427-023-2378-x

Source: Bioon Cells