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MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection 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 M...

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Autores principales: Tai, Wanbo, Zheng, Jian, Zhang, Xiujuan, Shi, Juan, Wang, Gang, Guan, Xiaoqing, Zhu, Jiang, Perlman, Stanley, Du, Lanying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278997/
https://www.ncbi.nlm.nih.gov/pubmed/37336390
http://dx.doi.org/10.1016/j.virusres.2023.199156
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author Tai, Wanbo
Zheng, Jian
Zhang, Xiujuan
Shi, Juan
Wang, Gang
Guan, Xiaoqing
Zhu, Jiang
Perlman, Stanley
Du, Lanying
author_facet Tai, Wanbo
Zheng, Jian
Zhang, Xiujuan
Shi, Juan
Wang, Gang
Guan, Xiaoqing
Zhu, Jiang
Perlman, Stanley
Du, Lanying
author_sort Tai, Wanbo
collection PubMed
description 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.
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spelling pubmed-102789972023-06-21 MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection Tai, Wanbo Zheng, Jian Zhang, Xiujuan Shi, Juan Wang, Gang Guan, Xiaoqing Zhu, Jiang Perlman, Stanley Du, Lanying Virus Res Article 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. Elsevier 2023-06-19 /pmc/articles/PMC10278997/ /pubmed/37336390 http://dx.doi.org/10.1016/j.virusres.2023.199156 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Tai, Wanbo
Zheng, Jian
Zhang, Xiujuan
Shi, Juan
Wang, Gang
Guan, Xiaoqing
Zhu, Jiang
Perlman, Stanley
Du, Lanying
MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection
title MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection
title_full MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection
title_fullStr MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection
title_full_unstemmed MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection
title_short MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection
title_sort mers-cov rbd-mrna vaccine induces potent and broadly neutralizing antibodies with protection against mers-cov infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278997/
https://www.ncbi.nlm.nih.gov/pubmed/37336390
http://dx.doi.org/10.1016/j.virusres.2023.199156
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