Monkeypox, a zoonotic disease, was first found in monkeys used in the study in 1958 and spread mainly in animals. Human monkeypox cases were first found in the Democratic Republic of the Congo in 1970. Since then, monkeypox has been endemic in a number of African countries, including Nigeria, the Democratic Republic of the Congo and the Central African Republic. Monkeypox cases outside Africa are usually caused by travel to Africa.
Monkeypox began to spread in Europe and North America in the first half of 2022, and on July 23, 2022, WHO Director—General Tan Desai declared the monkeypox outbreak a public health emergency of international concern (PHEIC). This is also the highest level of public health alert issued by the WHO to the world.
Recently, the Yan Jinghua research team of the Institute of Microbiology of the Chinese Academy of Sciences and Fang Min published a research paper entitled Mpox multi-antigen mRNA vaccine candidates by a simplified manufacturing strategy afford efficient protection against lethal orthopoxvirus challenge in the journal Emerging Microbes & Infections.
In this study, a monkeypox mRNA vaccine containing multiple antigens was developed, and the preparation process of multi-antigen mRNA vaccine was optimized.
In order to evaluate the immunogenicity of different antigens of monkeypox virus, the research team prepared mRNA vaccines from different antigens and immunized mice. The results showed that only M1 antigen induced high titer of neutralizing antibody. The composition of M1-induced antibody library was further analyzed, and the results showed that the antibodies targeting M1 were highly enriched and bound to the same epitope. If M1 is used alone as an antigen, there is a risk of escaping mutations, thus rendering the vaccine ineffective. Therefore, the researchers developed two multivalent mRNA candidate vaccines for monkeypox that encode four antigens (M1, A29, B6, and A35) or six antigens (M1, H3, A29, E8, B6, and A35).
The vaccine is prepared in two ways—one is to prepare a single antigen mRNA vaccine and then mix it (Lmix4/6), the other is to mix different vaccine DNA templates according to a certain proportion and translate and purify mRNA packaging in vitro (Rmix4/6) to simplify the preparation of a multi-antigen vaccine.
The team used a highly homologous smallpox virus vaccine strain—VACV to evaluate the immunogenicity and protective efficacy of the four vaccines in mice. The results showed that all the four vaccines could induce high titer neutralizing antibodies in a dose-dependent manner, and the serum neutralizing antibody in high dose group was significantly higher than that in the virus infected convalescent mice, and the cellular immune response induced by the 6-antigen vaccine was higher than that of the 4 antigen vaccine. In the challenge test of mice, the team immunized the mice with Lmix 4 + 6 or Rmix 4 + 6 vaccines, respectively, and then infected the mice with a lethal dose of VACV virus. The results showed that all the immunized groups completely protected the mice from virus infection, and there was no significant difference in the vaccines prepared by different methods.
These results fully suggest that the monkeypox mRNA vaccine containing the surface glycoproteins of the MV and EV viruses can induce strong humoral and cellular immunity and protect mice against a lethal dose of VACV infection. The simplified mRNA vaccine preparation process, starting with DNA template mixing, lays the foundation for future practical application.