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

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, ar...

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Main Authors: 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, Xiaoming Yang
Format: Article
Language:English
Published: Nature Portfolio 2023-09-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-41628-5
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author 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
Xiaoming Yang
author_facet 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
Xiaoming Yang
author_sort Fujun Hou
collection DOAJ
description 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.
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spelling doaj.art-a1ef86529e484fa7b1404a32b53e7fc62023-11-20T09:51:10ZengNature PortfolioNature Communications2041-17232023-09-0114111010.1038/s41467-023-41628-5mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challengeFujun Hou0Yuntao Zhang1Xiaohu Liu2Yanal M Murad3Jiang Xu4Zhibin Yu5Xianwu Hua6Yingying Song7Jun Ding8Hongwei Huang9Ronghua Zhao10William Jia11Xiaoming Yang12Shanghai Virogin Biotech Co. Ltd.CNBG-Virogin Biotech (Shanghai) Co. Ltd.Virogin Biotech Canada Ltd.Virogin Biotech Canada Ltd.Shanghai Virogin Biotech Co. Ltd.Shanghai Virogin Biotech Co. Ltd.Shanghai Virogin Biotech Co. Ltd.Shanghai Virogin Biotech Co. Ltd.Shanghai Virogin Biotech Co. Ltd.Shanghai Virogin Biotech Co. Ltd.Shanghai Virogin Biotech Co. Ltd.Shanghai Virogin Biotech Co. Ltd.China National Biotec Group Company Limited (CNBG)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.https://doi.org/10.1038/s41467-023-41628-5
spellingShingle 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
Xiaoming Yang
mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
Nature Communications
title mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
title_full mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
title_fullStr mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
title_full_unstemmed mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
title_short mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
title_sort mrna vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
url https://doi.org/10.1038/s41467-023-41628-5
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