mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge

Fujun Hou, Yuntao Zhang, Xiaohu Liu, Yanal M Murad, Jiang Xu, Zhibin Yu, Xianwu Hua, Yingying Song, Jun Ding, Hongwei Huang, Ronghua Zhao, William Jia () and Xiaoming Yang ()
Additional contact information
Fujun Hou: Shanghai Virogin Biotech Co. Ltd.
Yuntao Zhang: CNBG-Virogin Biotech (Shanghai) Co. Ltd.
Xiaohu Liu: Virogin Biotech Canada Ltd.
Yanal M Murad: Virogin Biotech Canada Ltd.
Jiang Xu: Shanghai Virogin Biotech Co. Ltd.
Zhibin Yu: Shanghai Virogin Biotech Co. Ltd.
Xianwu Hua: Shanghai Virogin Biotech Co. Ltd.
Yingying Song: Shanghai Virogin Biotech Co. Ltd.
Jun Ding: Shanghai Virogin Biotech Co. Ltd.
Hongwei Huang: Shanghai Virogin Biotech Co. Ltd.
Ronghua Zhao: Shanghai Virogin Biotech Co. Ltd.
William Jia: Shanghai Virogin Biotech Co. Ltd.
Xiaoming Yang: China National Biotec Group Company Limited (CNBG)

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: Abstract The recent outbreaks of mpox have raised concerns over the need for effective vaccines. However, the current approved vaccines have either been associated with safety concerns or are in limited supply. mRNA vaccines, which have shown high efficacy and safety against SARS-CoV-2 infection, are a promising alternative. In this study, three mRNA vaccines are developed that encode monkeypox virus (MPXV) proteins A35R and M1R, including A35R extracellular domain -M1R fusions (VGPox 1 and VGPox 2) and a mixture of encapsulated full-length mRNAs for A35R and M1R (VGPox 3). All three vaccines induce early anti-A35R antibodies in female Balb/c mice, but only VGPox 1 and 2 generate detectable levels of anti-M1R antibodies at day 7 after vaccination. However, all three mRNA vaccine groups completely protect mice from a lethal dose of vaccinia virus (VACV) challenge. A single dose of VGPox 1, 2, and 3 provide protection against the lethal viral challenge within 7 days post-vaccination. Long-term immunity and protection were also observed in all three candidates. Additionally, VGPox 2 provided better passive protection. These results suggest that the VGPox series vaccines enhance immunogenicity and can be a viable alternative to current whole-virus vaccines to defend against mpox.

Date: 2023
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DOI: 10.1038/s41467-023-41628-5

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