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An mpox quadrivalent mRNA vaccine protects mice from lethal vaccinia virus challenge
2024-10-09 125

 

Affiliations

  • Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China.
  • Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China.
  • MOE Key Laboratory for Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China.
  • MOE Key Laboratory for Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China. Electronic address: cwangust@ustc.edu.cn.
  • Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China. Electronic address: yucaiwang@ustc.edu.cn.
  • Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China; Core Unit of National Clinical Research Center for Laboratory Medicine, Hefei, Anhui, 230031, China; Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases, Hefei, Anhui, 230026, China. Electronic address: qiux@ustc.edu.cn.

PMID:  39089331 DOI: 10.1016/j.antiviral.2024.105974

Abstract

The outbreak of 2022 monkeypox virus (MPXV) infection in nonendemic regions is a global public health concern. A highly effective and safe MPXV vaccine that is available to the general public is urgently needed to control the mpox pandemic. Here, we developed a multivalent mRNA vaccine candidate, MPXV-1103, which expresses the full-length B6, A35, A29 and M1 proteins with three flexible linkers (G4S1)3in a single sequence. Compared with the monovalent MPXV mRNA vaccine candidates or the quadrivalent mRNA vaccine from mixtures of the four monovalent MPXV mRNA vaccines, MPXV-1103 elicits a robust humoral response and an MPXV-specific T-cell response and protects mice from lethal vaccinia virus (VACV) challenge, with no live virus detected in the nasal or lungs even at dosages as low as 1 μg. Furthermore, analysis of complete blood counts and photomicrographs of tissue from the main organs of mice vaccinated with MPXV-1103 at doses of 5 μg and 20 μg revealed that two doses of MPXV-1103 did not cause any observable pathological changes in the mice. Collectively, our results suggest that MPXV-1103, with features of high efficacy, safety and a simplified manufacturing process, is a promising vaccine candidate for defending against MPXV infection.

Keywords: Cellular immune responses; Humoral immune response; Monkeypox virus; Multivalent mRNA vaccine; Vaccinia virus.

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