دورية أكاديمية
Dendritic Cell-Mediated Cross-Priming by a Bispecific Neutralizing Antibody Boosts Cytotoxic T Cell Responses and Protects Mice against SARS-CoV-2.
| العنوان: | Dendritic Cell-Mediated Cross-Priming by a Bispecific Neutralizing Antibody Boosts Cytotoxic T Cell Responses and Protects Mice against SARS-CoV-2. |
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| المؤلفون: | Lázaro-Gorines R; Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, 28041, Spain.; Immuno-Oncology and Immunotherapy Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), Madrid, 28041, Spain.; H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, 28029, Spain., Pérez P; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, 28049, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, 28029, Spain., Heras-Murillo I; Immunobiology lab, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, 28029, Spain., Adán-Barrientos I; Immunobiology lab, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, 28029, Spain., Albericio G; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, 28049, Spain., Astorgano D; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, 28049, Spain., Flores S; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, 28049, Spain., Luczkowiak J; Virology and HIV/AIDS Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), Madrid, 28041, Spain., Labiod N; Virology and HIV/AIDS Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), Madrid, 28041, Spain., Harwood SL; Department of Molecular Biology and Genetics - Protein Science, Aarhus University, Aarhus, 80000, Denmark., Segura-Tudela A; Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, 28041, Spain.; Immuno-Oncology and Immunotherapy Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), Madrid, 28041, Spain.; H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, 28029, Spain., Rubio-Pérez L; Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, 28041, Spain.; Immuno-Oncology and Immunotherapy Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), Madrid, 28041, Spain.; H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, 28029, Spain.; Chair for Immunology UFV/Merck, Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcón, Madrid, 28223, Spain., Nugraha Y; Protein Crystallography Unit, Structural Biology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, 28029, Spain., Shang X; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, 20850, USA.; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Li Y; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, 20850, USA.; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.; The Center for Biomolecular Therapeutics, Rockville, MD, 20850, USA., Alfonso C; Centro de Investigaciones Biológicas Margarita Salas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, 28040, Spain., Adipietro KA; The Center for Biomolecular Therapeutics, Rockville, MD, 20850, USA.; Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Abeyawardhane DL; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, 20850, USA.; The Center for Biomolecular Therapeutics, Rockville, MD, 20850, USA.; Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Navarro R; Department of Antibody Engineering, Leadartis SL, Tres Cantos, Madrid, 28002, Spain., Compte M; Department of Antibody Engineering, Leadartis SL, Tres Cantos, Madrid, 28002, Spain., Yu W; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, 20850, USA., MacKerell AD Jr; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, 20850, USA.; Computer Aided Drug Design Center, Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, 21201, USA.; Center for Biomolecular Therapeutics (CBT), University of Maryland School of Medicine, Baltimore, MD 21201, USA., Sanz L; Molecular Immunology Unit, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, 28220, Spain., Weber DJ; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, 20850, USA.; The Center for Biomolecular Therapeutics, Rockville, MD, 20850, USA., Blanco FJ; Centro de Investigaciones Biológicas Margarita Salas (CIB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, 28040, Spain., Esteban M; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, 28049, Spain., Pozharski E; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, 20850, USA.; The Center for Biomolecular Therapeutics, Rockville, MD, 20850, USA., Godoy-Ruiz R; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, 20850, USA.; The Center for Biomolecular Therapeutics, Rockville, MD, 20850, USA., Muñoz IG; Protein Crystallography Unit, Structural Biology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, 28029, Spain., Delgado R; Virology and HIV/AIDS Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), Madrid, 28041, Spain.; Department of Microbiology, Hospital Universitario 12 de Octubre, Madrid, 28041, Spain.; Department of Medicine, Universidad Complutense de Madrid, Madrid, 28040, Spain., Sancho D; Immunobiology lab, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, 28029, Spain., García-Arriaza J; Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, 28049, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, 28029, Spain., Álvarez-Vallina L; Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, 28041, Spain.; Immuno-Oncology and Immunotherapy Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), Madrid, 28041, Spain.; H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, 28029, Spain.; Chair for Immunology UFV/Merck, Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcón, Madrid, 28223, Spain. |
| المصدر: | Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2023 Dec; Vol. 10 (34), pp. e2304818. Date of Electronic Publication: 2023 Oct 20. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Weinheim : WILEY-VCH, [2014]- |
| مواضيع طبية MeSH: | Antibodies, Neutralizing*/therapeutic use , COVID-19*, Mice ; Animals ; T-Lymphocytes, Cytotoxic ; SARS-CoV-2 ; Cross-Priming ; Dendritic Cells |
| مستخلص: | Administration of neutralizing antibodies (nAbs) has proved to be effective by providing immediate protection against SARS-CoV-2. However, dual strategies combining virus neutralization and immune response stimulation to enhance specific cytotoxic T cell responses, such as dendritic cell (DC) cross-priming, represent a promising field but have not yet been explored. Here, a broadly nAb, TN T , are first generated by grafting an anti-RBD biparatopic tandem nanobody onto a trimerbody scaffold. Cryo-EM data show that the TN T structure allows simultaneous binding to all six RBD epitopes, demonstrating a high-avidity neutralizing interaction. Then, by C-terminal fusion of an anti-DNGR-1 scFv to TN T , the bispecific trimerbody TN T DNGR-1 is generated to target neutralized virions to type 1 conventional DCs (cDC1s) and promote T cell cross-priming. Therapeutic administration of TN T DNGR-1, but not TN T , protects K18-hACE2 mice from a lethal SARS-CoV-2 infection, boosting virus-specific humoral responses and CD8 + T cell responses. These results further strengthen the central role of interactions with immune cells in the virus-neutralizing antibody activity and demonstrate the therapeutic potential of the Fc-free strategy that can be used advantageously to provide both immediate and long-term protection against SARS-CoV-2 and other viral infections. (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.) |
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| معلومات مُعتمدة: | R01 AI102766 United States AI NIAID NIH HHS; R01 AI126587 United States AI NIAID NIH HHS; R01 AI136756 United States AI NIAID NIH HHS; R41 AI147929 United States AI NIAID NIH HHS; R01 AI175439 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: CTL responses; SARS-CoV-2; bispecific trimerbody; cross-priming; dendritic cells; neutralizing antibody |
| المشرفين على المادة: | 0 (Antibodies, Neutralizing) |
| تواريخ الأحداث: | Date Created: 20231020 Date Completed: 20231211 Latest Revision: 20240823 |
| رمز التحديث: | 20240826 |
| مُعرف محوري في PubMed: | PMC10700188 |
| DOI: | 10.1002/advs.202304818 |
| PMID: | 37863812 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2198-3844 |
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| DOI: | 10.1002/advs.202304818 |