دورية أكاديمية
Single-shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad, durable and protective systemic and mucosal immunity in mice.
العنوان: | Single-shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad, durable and protective systemic and mucosal immunity in mice. |
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المؤلفون: | Cheang NYZ; Infectious Diseases Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore., Tan KS; Infectious Diseases Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Tan PS; Monash Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia., Purushotorma K; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Immunology Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Yap WC; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore., Tullett KM; Monash Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia., Chua BYL; Immunology Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Yeoh AY; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore., Tan CQH; Histology Core Facility, Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore., Qian X; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Immunology Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Chen H; Infectious Diseases Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Tay DJW; Infectious Diseases Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Caminschi I; Monash Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia; Department of Microbiology and Immunology, Peter Doherty Institute, The University of Melbourne, Melbourne, VIC, Australia., Tan YJ; Infectious Diseases Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Macary PA; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Immunology Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Tan CW; Infectious Diseases Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Lahoud MH; Monash Biomedicine Discovery Institute & Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia., Alonso S; Infectious Diseases Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore. Electronic address: micas@nus.edu.sg. |
المصدر: | Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2024 Jul 03; Vol. 32 (7), pp. 2299-2315. Date of Electronic Publication: 2024 May 06. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-0024 (Electronic) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2017- : Cambridge, MA : Cell Press Original Publication: San Diego, CA : Academic Press, 2000- |
مواضيع طبية MeSH: | Dendritic Cells*/immunology , SARS-CoV-2*/immunology , COVID-19*/prevention & control , COVID-19*/immunology , COVID-19*/virology , Immunity, Mucosal* , COVID-19 Vaccines*/immunology , Lectins, C-Type*/immunology , Lectins, C-Type*/metabolism , Antibodies, Viral*/immunology , Antibodies, Neutralizing*/immunology, Animals ; Mice ; Humans ; Female ; Spike Glycoprotein, Coronavirus/immunology ; Receptors, Mitogen/immunology ; Antibody-Dependent Cell Cytotoxicity/immunology ; Receptors, Immunologic |
مستخلص: | Current coronavirus disease 2019 vaccines face limitations including waning immunity, immune escape by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, limited cellular response, and poor mucosal immunity. We engineered a Clec9A-receptor binding domain (RBD) antibody construct that delivers the SARS-CoV-2 RBD to conventional type 1 dendritic cells. Compared with non-targeting approaches, single dose immunization in mice with Clec9A-RBD induced far higher RBD-specific antibody titers that were sustained for up to 21 months after vaccination. Uniquely, increasing neutralizing and antibody-dependent cytotoxicity activities across the sarbecovirus family was observed, suggesting antibody affinity maturation over time. Consistently and remarkably, RBD-specific follicular T helper cells and germinal center B cells persisted up to 12 months after immunization. Furthermore, Clec9A-RBD immunization induced a durable mono- and poly-functional T-helper 1-biased cellular response that was strongly cross-reactive against SARS-CoV-2 variants of concern, including Omicron subvariants, and with a robust CD8 + T cell signature. Uniquely, Clec9A-RBD single-shot systemic immunization effectively primed RBD-specific cellular and humoral immunity in lung and resulted in significant protection against homologous SARS-CoV-2 challenge as evidenced by limited body weight loss and approximately 2 log Competing Interests: Declaration of interests M.H.L., I.C., and K.M.T. are listed as inventors on patents relating to Clec9A antibodies. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
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فهرسة مساهمة: | Keywords: COVID-19; Clec9A; antibody-dependent cytotoxicity; dendritic cell targeting; mucosal immunity; receptor binding domain; sarbecoviruses |
المشرفين على المادة: | 0 (COVID-19 Vaccines) 0 (Lectins, C-Type) 0 (Antibodies, Viral) 0 (Antibodies, Neutralizing) 0 (Clec9a protein, mouse) 0 (Spike Glycoprotein, Coronavirus) 0 (Receptors, Mitogen) 0 (Receptors, Immunologic) |
SCR Organism: | SARS-CoV-2 variants |
تواريخ الأحداث: | Date Created: 20240508 Date Completed: 20240704 Latest Revision: 20240801 |
رمز التحديث: | 20240801 |
مُعرف محوري في PubMed: | PMC11286822 |
DOI: | 10.1016/j.ymthe.2024.05.003 |
PMID: | 38715364 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1525-0024 |
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DOI: | 10.1016/j.ymthe.2024.05.003 |