Multivalent mRNA vaccine platform with compatible antigens conferred broad-spectrum protection against orthoebolaviruses’ exposure
Abstract
Several orthoebolaviruses have been established, including Orthoebolavirus zairense [for Ebola virus (EBOV)], Orthoebolavirus sudanense [for Sudan virus (SUDV)], and Orthoebolavirus bundibugyoense [for Bundibugyo virus (BDBV)]. Orthoebolaviruses are highly virulent pathogens that cause severe disease in humans. However, most existing vaccines primarily target EBOV, and fail to provide robust cross-protection against other lethal orthoebolaviruses. The development of a broad-spectrum vaccine has the potential to efficiently mitigate outbreaks caused by multiple orthoebolaviruses. In this study, we developed and evaluated a broad-spectrum mRNA vaccine, designated [GPs+NP]@LNP, formulated with a single lipid nanoparticle (LNP) platform to encapsulate a mixed mRNA payload encoding the glycoproteins (GPs) of EBOV, BDBV, and SUDV, along with the nucleoprotein (NP) of EBOV. This rational antigenic combination was designed to engage both humoral and cellular arms of the immune system. Consistent with this design, the compatibility of humoral immunity-driving GPs and cellular immune-dominating NPs supports complementary immune responses, which together are associated with broad and durable protection against EBOV, BDBV, and SUDV in animal models. Antigenic coordination within a single LNP formulation may therefore represent an effective strategy to optimize vaccine immunogenicity, protective effect, durability, and safety. Collectively, these findings highlight [GPs+NP]@LNP as a promising approach for the development of next-generation vaccines targeting multiple pathogenic orthoebolaviruses.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (20)
Jiachen Zhang
Department of Infectious Disease, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Xinghai Zhang
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences
Yanfeng Yao
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences
Junhui Zhou
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences
Da Chen
Ministry of Education Key Laboratory for Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China
Yanqiong Shen
Division of Life Sciences and Medicine, University of Science and Technology of China
Qizan Gong
Division of Life Sciences and Medicine, University of Science and Technology of China
Zhihao Li
Zunhao Zhou
Division of Life Sciences and Medicine, University of Science and Technology of China
Entao Li
Division of Life Sciences and Medicine, University of Science and Technology of China
Fangxu Li
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences
Zekai Cheng
Division of Life Sciences and Medicine, University of Science and Technology of China
Yang Liu
Weiqi Wang
Division of Life Sciences and Medicine, University of Science and Technology of China
Hang Liu
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay
Miaoyu Chen
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences
Huajun Zhang
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences
Chao Wang
Yucai Wang
State Key Laboratory of Immune Response and Immunotherapy, Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine
Sandra Chiu
Department of Infectious Disease, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China