Mpox virus mRNA-lipid nanoparticle vaccine candidates evoke antibody responses and drive protection against the Vaccinia virus challenge in mice

In response to the human Mpox (hMPX) epidemic that began in 2022, there is an urgent need for a monkeypox vaccine. Here, we have developed a series of mRNA-lipid nanoparticle (mRNA-LNP)-based vaccine candidates that encode a collection of four highly conserved Mpox virus (MPXV) surface proteins invo...

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Bibliographic Details
Published in:Antiviral research 2023-08, Vol.216, p.105668-105668, Article 105668
Main Authors: Xia, Heng, He, Yun-Ru, Zhan, Xiao-Yong, Zha, Gao-Feng
Format: Article
Language:English
Subjects:
Animals
Antibodies, Viral
Antibody Formation
Antibody responses
Humans
Mice
Monkeypox virus
Mpox (monkeypox) - prevention & control
Mpox virus
mRNA vaccines
mRNA-lipid nanoparticle
Vaccinia virus - genetics
Viral Envelope Proteins - genetics
Viral Vaccines
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Summary:In response to the human Mpox (hMPX) epidemic that began in 2022, there is an urgent need for a monkeypox vaccine. Here, we have developed a series of mRNA-lipid nanoparticle (mRNA-LNP)-based vaccine candidates that encode a collection of four highly conserved Mpox virus (MPXV) surface proteins involved in virus attachment, entry, and transmission, namely A29L, A35R, B6R, and M1R, which are homologs to Vaccinia virus (VACV) A27, A33, B5, and L1, respectively. Despite possible differences in immunogenicity among the four antigenic mRNA-LNPs, administering these antigenic mRNA-LNPs individually (5 μg each) or an average mixture of these mRNA-LNPs at a low dose (0.5 μg each) twice elicited MPXV-specific IgG antibodies and potent VACV-specific neutralizing antibodies. Furthermore, two doses of 5 μg of A27, B5, and L1 mRNA-LNPs or a 2 μg average mixture of the four antigenic mRNA-LNPs protected mice against weight loss and death after the VACV challenge. Overall, our data suggest that these antigenic mRNA-LNP vaccine candidates are both safe and efficacious against MPXV, as well as diseases caused by other orthopoxviruses. •mRNA-LNP targets A27, L1, A33 and B5 of monkeypox virus can induce potent humoral immunity in mice.•The four antigenic mRNA-LNPs protect mice from the VACV challenge.•The monkeypox mRNA-LNPs vaccines gain a safe evaluation in mice.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2023.105668