Recently, SCIENCE CHINA Life Sciences published a collaborative research paper entitled “Multi-valent mRNA vaccines against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity”.
In this study, EV and MV specific surface antigens were chosen to design and make different combinations of multivalent mRNA vaccines, such as EV antigen (2 valence), MV antigen (2 and 4 valence), and EV and MV mixed antigen (6 valence). Through animal immunization and virus infection experiments, we found different immunogenicity and immune neutralization abilities of two kinds of virus particle surface antigens of monkeypox virus, EV and MV, which revealed the enhanced resistance mechanism of the multivalent mRNA vaccine against monkeypox virus. It laid the foundation for further development of an efficient and safe mRNA vaccine and enhancement of resistance to the monkeypox virus epidemic outbreak.
Monkeypox virus (MPV) was first found in non-human primates in Africa in the 1950s. Human monkeypox virus infection was first diagnosed in the Republic of Congo in the 1970s, causing lesions similar to smallpox. Since then, the monkeypox virus has spread across the African continent, mainly in Central and West Africa. In recent years, with the increase of human-to-human transmission, the epidemic scale of monkeypox virus infection is expanding all over the world. In July 2022, the World Health Organization declared the monkeypox outbreak a global health emergency of international concern. As of March 2023, more than 86,000 confirmed cases and more than 110 deaths had been reported in 110 countries. In the face of the threat of monkeypox epidemic, it is urgent to develop a specific vaccine against the monkeypox virus to prevent the transmission and spread of the virus.
Monkeypox virus belongs to a large family of double-stranded DNA viruses, including varicella virus, smallpox virus, and vaccinia virus (VACV). Viruses producing two different forms of virus particles during their replication cycle are enveloped virus (EV) and mature virus (MV). Based on the population immunity study of other orthopoxviruses and the simulation calculation of the surface protein of monkeypox virus, the researchers selected the specific surface antigens of EV and MV, and designed and prepared different combinations of multivalent mRNA vaccines, such as EV-antigen, MV-antigen, and mixed antigen of EV and MV, in order to study the efficacy and safety of various multivalent mRNA vaccines.
It was found that the multivalent mRNA vaccine prepared by different combinations of antigens could strongly induce a specific IgG immune response in mice inoculated with various surface antigens, but different antigens had different kinetics and reaction intensities. At the same time, there was a good correlation between the virus neutralizing activity and the total IgG antibody level in the sera of mice immunized with different antigens. The study also found that the immune response of mice inoculated with monkeypox virus mRNA vaccine is through the induction of an antigen-specific CD4+ T lymphocyte reaction, and this immune response is dependent on Th1 cells.
In the VACV challenge test of immunized mice, it was found that after immunized mice were infected with a lethal dose of VACV virus, four different mRNA polyvalent vaccines could protect mice from virus infection, and their protective ability was positively correlated with the total IgG response of mice. The hexavalent mRNA vaccine combined with two types of virus particle (EV+MV) antigens provides the best protection. In contrast, mice in the control group (injected with a placebo vaccine) were not protected.
The above studies showed that using the mRNA vaccine with the combination of surface antigens of EV/MV virus particles selected by calculation and analysis, we found that the two kinds of surface antigens of monkeypox virus had different immunogenicity and immune neutralization abilities, which revealed the enhanced resistance mechanism of the multivalent mRNA vaccine against monkeypox virus. The study provides an analysis of the mechanism and kinetics of different monkeypox virus surface antigens and their induction of immune responses in vivo. The model of mice challenged with a lethal dose of VACV was used to verify the effectiveness of multivalent mRNA vaccine in immunized mice. The multivalent mRNA vaccine in this study has no toxic reaction in immunized mice and has good safety. It laid the foundation for further development of an efficient and safe mRNA vaccine and enhancement of resistance to the monkeypox virus epidemic outbreak.