MERS-CoV RBD-mRNA Presents Better Immunogenicity and Protection than the Spike-mRNA

Qian Liu; Abhishek K Verma; Xiaoqing Guan; Shengnan Qian; Stanley Perlman; Lanying Du

doi:10.3390/cells14231928

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MERS-CoV RBD-mRNA Presents Better Immunogenicity and Protection than the Spike-mRNA

Journal article

Open access

Peer reviewed

MERS-CoV RBD-mRNA Presents Better Immunogenicity and Protection than the Spike-mRNA

Qian Liu, Abhishek K Verma, Xiaoqing Guan, Shengnan Qian, Stanley Perlman and Lanying Du

Cells (Basel, Switzerland), Vol.14(23), 1928

12/04/2025

DOI: 10.3390/cells14231928

PMCID: PMC12691421

PMID: 41369417

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https://doi.org/10.3390/cells14231928View

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Abstract

Pathogenic Middle East respiratory syndrome CoV (MERS-CoV), first identified in Saudi Arabia in 2012, continues to pose a threat to public health. The trimeric spike (S) protein of MERS-CoV binds to the cellular receptor through the receptor-binding domain (RBD) in the S1 subunit to initiate virus entry and infection. Therefore, both the S protein and its RBD are targets for the development of MERS-CoV vaccines. Nevertheless, a direct comparison of the immune efficiency of S- and RBD-based MERS-CoV vaccines has not been made. Here, we compared two mRNA vaccines, respectively, targeting the S (S-mRNA) and RBD (RBD-mRNA) of MERS-CoV for their durable immunogenicity, neutralizing activity, and protective efficacy in a mouse model. Both mRNAs encapsulated with lipid nanoparticles (LNPs) maintained strong stability at various temperatures during the detection period. LNP-encapsulated RBD-mRNA elicited significantly higher and more durable antibodies than LNP-encapsulated S-mRNA, maintaining stronger and broadly neutralizing activity against the MERS-CoV original strain, as well as multiple variants containing key mutations within the RBD region. Importantly, RBD-mRNA provided durable protective efficacy against MERS-CoV infection in middle-aged mice, and this protection was associated positively with serum neutralizing antibody titers. Overall, this study identifies RBD-mRNA as an effective vaccine against MERS-CoV, with great potential for further development.

Animals

Antibodies, Neutralizing - immunology

Antibodies, Viral - immunology

Coronavirus Infections - immunology

Coronavirus Infections - prevention & control

Coronavirus Infections - virology

Female

Humans

Immunogenicity, Vaccine

Mice

Mice, Inbred BALB C

Middle East Respiratory Syndrome Coronavirus - genetics

Middle East Respiratory Syndrome Coronavirus - immunology

Nanoparticles - chemistry

RNA, Messenger - genetics

RNA, Messenger - immunology

Spike Glycoprotein, Coronavirus - genetics

Spike Glycoprotein, Coronavirus - immunology

Viral Vaccines - immunology

Details

Title: Subtitle: MERS-CoV RBD-mRNA Presents Better Immunogenicity and Protection than the Spike-mRNA
Creators: Qian Liu - Georgia State University
Abhishek K Verma - University of Iowa
Xiaoqing Guan - Georgia State University
Shengnan Qian - Georgia State University
Stanley Perlman - University of Iowa
Lanying Du - Georgia State University
Resource Type: Journal article
Publication Details: Cells (Basel, Switzerland), Vol.14(23), 1928
DOI: 10.3390/cells14231928
PMID: 41369417
PMCID: PMC12691421
NLM abbreviation: Cells
ISSN: 2073-4409
eISSN: 2073-4409
Publisher: MDPI
Grant note: 5R01AI139092-06A0 / NIH HHS 5R01AI137472-06A0 / NIH HHS
Language: English
Date published: 12/04/2025
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9985090591502771

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