In the study published in the journal SCIENCE CHINA Life Sciences on June 1, 2023, entitled Multi-valent mRNA vaccines against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity, Prof. HAO Pei’s group at the Shanghai Institute of Immunity and Infection of the Chinese Academy of Sciences, Prof. LI Xiao at Changchun Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Prof. LI Xuan at Institute of Plant Physiology and Ecology of the Chinese Academy of Sciences, and Prof. ZHONG Wu at National Engineering Research Center for the Emergency Drug of Beijing Institute of Pharmacology and Toxicology reported their new research.

Monkeypox virus (MPV) was first identified in non-human primates in Africa in the 1950s.The first confirmed human infection with MPV in the 1970s resulted in smallpox-like lesions. In July 2022, the World Health Organization declared the monkeypox outbreak an epidemic of international concern and a global health emergency. Monkeypox was declared a global health emergency by the World Health Organization, and as of March 2023, 86,000 confirmed cases and 111 deaths across 110 countries have been reported.

Its causal agent, monkeypox virus (MPV) belongs to a large family of double-stranded DNA viruses, Orthopoxviridae, that also includes vaccinia virus (VACV) and others. MPV produces two distinct forms of viral particles during its replication cycles: the enveloped viron (EV) that is released via exocytosis, and the mature viron (MV) that is discharged through lysis of host cells.

This study was designed to develop multi-valent mRNA vaccines against monkeypox EV and MV surface proteins, and examine their efficacy and mechanism of action. Four mRNA vaccines were produced with different combinations of surface proteins from EV (A35R and B6R), MV (A29L, E8L, H3L and M1R), or EV and MV, and were administered in Balb/c mice to assess their immunogenicity potentials.

Further, the mRNA vaccines elicited an antigen-specific CD4+ T cell response that is biased towards Th1. The mRNA vaccines with different combinations of EV and MV surface antigens protected a mouse model from a lethal dose VACV challenge, with the EV and MV antigens-combined vaccine offering the strongest protection.

These findings provide insight into the protective mechanism of multi-valent mRNA vaccines against MPV, and also the foundation for further development of effective and safe mRNA vaccines for enhanced protection against monkeypox virus outbreak.

                                     Design of mRNA vaccines and characterization of surface antigens against monkeypox virus. (Image by SIII)

                                               mRNA vaccine induces potent IgG and neutralizing antibody responses in mice (Image by SIII)

Contact

HAO Pei

Shanghai Institute of Immunity and Infection, CAS

E-mail: phao@siii.cas.cn

Reference:  https://link.springer.com/article/10.1007/s11427-023-2378-x#author-information