Rational development of multicomponent mRNA vaccine candidates against mpox
Open Access
- 31 March 2023
- journal article
- research article
- Published by Taylor & Francis Ltd in Emerging Microbes & Infections
- Vol. 12 (1), 2192815
- https://doi.org/10.1080/22221751.2023.2192815
Abstract
The re-emerging mpox (formerly monkeypox) virus (MPXV), a member of Orthopoxvirus genus together with variola virus (VARV) and vaccinia virus (VACV), has led to public health emergency of international concern since July, 2022. Inspired by the unprecedent success of coronavirus disease 2019 (COVID-19) mRNA vaccines, the development of a safe and effective mRNA vaccine against MPXV is of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we rationally constructed and prepared a panel of multicomponent MPXV vaccine candidates encoding different combinations of viral antigens including M1R, E8L, A29L, A35R and B6R. In vitro and in vivo characterization demonstrated that two immunizations of all mRNA vaccine candidates elicit a robust antibody response as well as antigen specific Th1-biased cellular response in mice. Importantly, the penta- and tetra-component vaccine candidates AR-MPXV5 and AR-MPXV4a showed superior capability of inducing neutralizing antibodies as well as of protecting from VACV challenge in mice. Our study provides critical insights to understand the protection mechanism of MPXV infection and direct evidence supporting further clinical development of these multicomponent mRNA vaccine candidates.Keywords
Funding Information
- National Key Research and Development Project of China (2021YFC2302400)
- National Natural Science Foundation of China (82241069)
- National Science Fund for Distinguished Young Scholars (81925025, 81621005, 2019-I2M-5-049)
- Chinese Academy of Medical Sciences
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