Cited by 153SARS-CoV-2 and COVID-19 ResearchSARS-CoV-2 detection and testingvaccines and immunoinformatics approaches

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A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2

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Tai, Wanbo, Zhang, Xiujuan, Drelich, Aleksandra, Shi, Juan, Hsu, Jason C., Luchsinger, Larry, Hillyer, Christopher D., Tseng, Chien-Te K., Jiang, Shibo, Du, Lanying·2020·Cell Research

DOI 10.1038/s41422-020-0387-5PMC PMC7403570

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Abstract

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need to develop effective and safe vaccines. Similar to SARS-CoV, SARS-CoV-2 recognizes angiotensin-converting enzyme 2 (ACE2) as receptor for host cell entry. 1 , 2 SARS-CoV-2 spike (S) protein consists of S1, including receptor-binding domain (RBD), and S2 subunits. 3 , 4 We previously demonstrated that RBDs of SARS-CoV and MERS-CoV serve as important targets for the development of effective vaccines. 5 , 6

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Fig. 1 Design and evaluation of SARS-CoV-2 S1 and RBD mRNA vaccines. a Schematic diagram of SARS-CoV-2 S1 and RBD mRNA construction. The synthesized nucleoside-modified S1 and RBD mRNAs were encapsulated with LNPs to form mRNA-LNPs. b–j IgG and neutralizing antibodies induced in immunized BALB/c mice at different immunogen doses via intradermal (I.D.) prime and boost at 4 weeks. Sera at 10 days post-2nd immunization with SARS-CoV-2 S1 or RBD mRNA-LNP (e.g., S1-LNP or RBD-LNP) (30 μg/mouse), or empty LNP (control), were detected for SARS-CoV-2 RBD-specific IgG antibodies by ELISA (b) or neutralizing antibodies against pseudotyped (c) and live (d) SARS-CoV-2 infection. Sera at 10, 40, and 70 days post-2nd immunization with above mRNA-LNPs (10 μg/mouse) or control were detected for neutralizing antibodies against pseudotyped (e–g) and live (h–j) SARS-CoV-2 infection. The ELISA plates were coated with SARS-CoV-2 RBD-Fc protein (1 µg/ml), and IgG antibody (Ab) titer was calculated. Overall, 50% neutralizing antibody titer (nAb NT50) was calculated against SARS-CoV-2 pseudovirus infection in hACE2/293T cells, or against live SARS-CoV-2 infection by a cytopathic effect (CPE)-based microneutralization assay in Vero E6 cells. The dotted lines indicate detection limit. k Dose-dependent inhibition of sera of mice receiving a vaccine (30 μg/mouse) on SARS-CoV-2 RBD-hACE2 receptor binding in hACE2/293T cells by flow cytometry analysis. Percent (%) inhibition was calculated based on relative fluorescence intensity with or without respective serum at indicated dilutions. l–n Representative images of such inhibition by sera (1:5) of mice immunized with SARS-CoV-2 S1 mRNA-LNP (S1-LNP) (l), RBD mRNA-LNP (RBD-LNP) (m), or empty LNP control (n) are shown in blue lines with respective median fluorescence intensity (MFI) values. The binding between SARS-CoV-2 RBD-Fc protein (5 µg/mL) and hACE2 is shown in red lines. Gray shades indicate Fc-hACE2 binding. o Cross-reactivity of immunized mouse sera against SARS-CoV RBD by ELISA. SARS-CoV RBD-Fc protein-coated plates (1 µg/mL) were used to detect IgG Ab titer. p–r Cross nAb NT50 of above sera (twofold serial dilutions from 1:5) against infection of SARS-CoV pseudovirus expressing S protein of human SARS-CoV strains Tor2 (p) and GD03 (q), or palm civet SARS-CoV strain SZ3 (r) in hACE2/293T cells. Data (b, c, e–g, k–r) are presented as means ± SEM of mice (n = 5); data (d, h–j) are presented as means ± SEM of duplicate wells of pooled sera from five mice per group. Significant differences are shown as *P < 0.05; **P < 0.01; ***P < 0.001. Experiments were repeated twice with similar results.CC BY · PubMed Central

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Authors: Tai, W., Zhang, X., Drelich, A., Shi, J., Hsu, J. C., Luchsinger, L., Hillyer, C. D., Tseng, C.-T. K., Jiang, S., & Du, L.
Affiliations: New York Blood Center (US)
The University of Texas Medical Branch at Galveston (US)
Corresponding author: Jiang, Shibo
Du, Lanying
ORCID: Tai, Wanbo
Zhang, Xiujuan
Drelich, Aleksandra
Shi, Juan
Hsu, Jason C.
Luchsinger, Larry
Tseng, Chien-Te K.
Jiang, Shibo
Du, Lanying
Venue: Cell Research
Publisher: Springer Science and Business Media LLC
Published: 2020-08-05
Volume: 30
Issue: 10
Pages: 932-935
ISSN: 1001-0602 (ISSN-L)
1748-7838
DOI: 10.1038/s41422-020-0387-5
PMC: PMC7403570
OpenAlex: W3046985131
Cited by: 151
References: 12
Citations by year: 2026: 6 · 2025: 10 · 2024: 15 · 2023: 20 · 2022: 41 · 2021: 48 · 2020: 11
FWCI: 3.94
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Cell Research (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: U.S. Department of Health and Human Services (R01AI137472, R01AI139092)
National Institutes of Health
National Institute of Allergy and Infectious Diseases (R01AI137472, R01AI139092, R01AI157975)
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords: SARS-CoV-2, COVID-19 pandemic, mRNA vaccines, receptor binding domain, spike protein, ACE2 receptor, vaccine design, coronavirus vaccines
MeSH terms: Protein Domains, Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Animals, Cell Line, Humans, Immunization, Mice, Inbred BALB C, Pneumonia, Viral, RNA, Messenger, Viral Vaccines, Gene Expression, Coronavirus Infections, Antibodies, Neutralizing, Pandemics, Spike Glycoprotein, Coronavirus

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A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2

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