Newswise — A breakthrough has been achieved by a collaborative team of researchers hailing from the Chinese Academy of Sciences, the Chinese Academy of Agricultural Sciences, and the Beijing Institute of Pharmacology and Toxicology. Their remarkable progress centers around the development of multi-valent mRNA vaccines specifically designed to combat the monkeypox virus (MPV), an agent known to cause a disease resembling smallpox in humans. The team's study demonstrated that these multi-valent mRNA vaccines, incorporating various combinations of monkeypox enveloped viron (EV) or mature viron (MV) surface antigens, elicited dynamic immune responses characterized by a strong IgG response and accompanying neutralizing activities. Crucially, these vaccines successfully shielded a mouse model from a lethal dose of vaccinia virus (VACV) when subjected to a challenging test.
The findings of this study have been published online in Science China Life Sciences, shedding light on the intricate mechanisms behind the protective effects of multi-valent mRNA vaccines. These discoveries not only deepen our understanding of how these vaccines work but also serve as valuable support for the advancement of efficient and secure mRNA vaccines, capable of providing enhanced protection against potential monkeypox virus outbreaks.
Monkeypox, a virus that shares similarities with smallpox and affects humans, was initially discovered in African non-human primates during the 1950s. In recent times, there has been a concerning rise in cases of human-to-human transmission, leading to a widespread epidemic of monkeypox virus infection across multiple countries worldwide. The gravity of the situation prompted the World Health Organization to declare monkeypox as a global health emergency in July 2022. This declaration reflects the urgent need for international attention and collaborative efforts to address the growing threat posed by monkeypox and its escalating impact on public health.
Initially, the researchers concentrated on identifying the crucial viral proteins necessary for vaccine development. They selected six surface proteins from MPV, consisting of two from EV (A35R and B6R) and four from MV (A29L, E8L, H3L, and M1R). These choices were based on previous studies conducted on other orthopoxviruses and an in silico computation analysis to evaluate the immunogenic potential of MPV surface proteins.
To evaluate the safety and effectiveness of the vaccines, which contained either EV-only, MV-only, or a combination of EV and MV antigens, they administered them to Balb/c mice. Within seven days of the initial immunization, a dynamic immune response was observed. Additionally, the second immunization significantly enhanced the antibody responses for all the EV- and MV-surface antigens.
In addition, the researchers discovered that the combination of EV and MV immunogens in the vaccines resulted in a stronger overall IgG response and corresponding neutralizing activity against VACV. This finding suggests that each immunogen contributed additively to the generation of immune responses and the prevention of VACV infection. Moreover, the mRNA vaccines were found to stimulate a specific CD4+ T cell response against the antigens, which exhibited a bias towards Th1 immunity.
Dr. Pei Hao, the principal researcher of the collaborative study and senior author of the published paper, expressed their amazement at the results. In a mouse model exposed to a lethal dose of VACV, all the mice that received the mRNA vaccines, regardless of the combinations of EV and MV surface antigens, survived the VACV infection. Dr. Hao emphasized that the vaccine combining EV and MV surface antigens (MPV-EM6) provided the strongest protection, which aligned excellently with the robust total IgG response and corresponding neutralizing activity against VACV. This outcome serves as a positive indication that the multi-valency approach employed in the study has proven to be successful.
The rapid response time and adaptability of mRNA vaccines make them an unparalleled platform for the swift development and deployment of vaccines in the face of pathogenic outbreaks. This study underscores the importance of mRNA vaccines in combating such outbreaks, with a specific focus on developing multi-valent mRNA vaccines targeting the monkeypox virus. The findings of this study provide valuable insights into the protective mechanisms of multi-valent mRNA vaccines and establish a foundation for future efforts to develop effective and safe mRNA vaccines that offer enhanced protection against monkeypox virus outbreaks.
Funding for this research was provided by various sources, including the National Science and Technology Major Projects, the National Key Research and Development Program of China, the Priority Research Program of the Chinese Academy of Sciences, the Shanghai Municipal Science and Technology Major Project, and the National Natural Science Foundation of China. These funding sources played a crucial role in supporting the study and its findings.
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