MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection

Wanbo Tai; Jian Zheng; Xiujuan Zhang; Juan Shi; Gang Wang; Xiaoqing Guan; Jiang Zhu; Stanley Perlman; Lanying Du

doi:10.1016/j.virusres.2023.199156

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MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection

Journal article

Open access

Peer reviewed

MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection

Wanbo Tai, Jian Zheng, Xiujuan Zhang, Juan Shi, Gang Wang, Xiaoqing Guan, Jiang Zhu, Stanley Perlman and Lanying Du

Virus research, Vol.334, 199156

06/19/2023

DOI: 10.1016/j.virusres.2023.199156

PMCID: PMC10278997

PMID: 37336390

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Abstract

•LNP-encapsulated modified MERS-CoV RBD-mRNA presents high stability.•It induced potent neutralizing antibodies against divergent MERS-CoV strains.•Intradermal route elicited the highest anti-MERS-CoV neutralizing antibody titer.•This vaccine completely protected immunized mice against MERS-CoV infection. Middle East respiratory syndrome coronavirus (MERS-CoV), a highly pathogenic coronavirus in the same Betacoronavirus genus and Coronaviridae family as SARS-CoV-2, continues to post a threat to human health. Mortality remains high; therefore, there is a need to develop effective vaccines to prevent MERS-CoV infection. The receptor-binding domain (RBD) within the MERS-CoV spike (S) protein is a critical vaccine target. The latest mRNA technology has enabled rapid development of much-needed vaccines with high efficiency and scalable manufacturing capacity. Here, we designed a mRNA vaccine encoding the RBD of MERS-CoV S protein (RBD-mRNA) and evaluated its immunogenicity and protective efficacy in a mouse model. The data showed that nucleoside-modified RBD-mRNA, but not RBD-mRNA lacking the nucleoside modification, was stable and elicited broadly and durable neutralizing antibody and cellular immune responses, which neutralized the original strain and multiple MERS-CoV variants. Among all immunization routes tested, the intradermal route was appropriate for this RBD-mRNA to induce strong B-cell responses and the highest neutralizing antibody titers. Importantly, injection of nucleoside-modified RBD-mRNA through the intradermal route protected immunized mice against challenge with MERS-CoV. This protection correlated with serum neutralizing antibody titers. Overall, we have developed an effective MERS-CoV RBD-based mRNA vaccine (with potential for further development) that prevents infection by divergent strains of MERS-CoV.

Coronavirus

MERS-CoV

mRNA vaccine

Neutralizing antibody, Protection

Receptor-binding domain

Spike protein

Details

Title: Subtitle: MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection
Creators: Wanbo Tai - New York Blood Center
Jian Zheng - University of Iowa
Xiujuan Zhang - New York Blood Center
Juan Shi - New York Blood Center
Gang Wang - Georgia State University
Xiaoqing Guan - Georgia State University
Jiang Zhu - Scripps Research Institute
Stanley Perlman - University of Iowa
Lanying Du - New York Blood Center
Resource Type: Journal article
Publication Details: Virus research, Vol.334, 199156
DOI: 10.1016/j.virusres.2023.199156
PMID: 37336390
PMCID: PMC10278997
NLM abbreviation: Virus Res
ISSN: 0168-1702
eISSN: 1872-7492
Publisher: Elsevier B.V
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: R01AI137472, R01AI139092, R01AI157975
Language: English
Date published: 06/19/2023
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9984436460202771

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