دورية أكاديمية
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A Small Molecule RIG-I Agonist Serves as an Adjuvant to Induce Broad Multifaceted Influenza Virus Vaccine Immunity.

التفاصيل البيبلوغرافية
العنوان: A Small Molecule RIG-I Agonist Serves as an Adjuvant to Induce Broad Multifaceted Influenza Virus Vaccine Immunity.
المؤلفون: Hemann EA; Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA.; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH., Knoll ML; Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA., Wilkins CR; Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA., Subra C; The Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Military HIV Research Program, Bethesda, MD., Green R; Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA., García-Sastre A; The Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Military HIV Research Program, Bethesda, MD.; Department of Microbiology, The Tisch Cancer Institute, Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY.; Department of Pathology, Molecular and Cell-Based Medicine, The Tisch Cancer Institute, Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Thomas PG; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN., Trautmann L; The Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Military HIV Research Program, Bethesda, MD.; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR., Ireton RC; Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA., Loo YM; Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA., Gale M Jr.; Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA.
المصدر: Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2023 May 01; Vol. 210 (9), pp. 1247-1256.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE
أسماء مطبوعة: Publication: Bethesda, MD : American Association of Immunologists
Original Publication: Baltimore : Williams & Wilkins, c1950-
مواضيع طبية MeSH: Influenza Vaccines* , Influenza A Virus, H5N1 Subtype*/metabolism , Influenza, Human* , Influenza A virus*, Humans ; Animals ; Mice ; DEAD Box Protein 58/metabolism ; Interferon Regulatory Factor-3/metabolism ; Adjuvants, Immunologic ; Antiviral Agents/pharmacology ; Immunity, Innate
مستخلص: Retinoic acid-inducible gene I (RIG-I) is essential for activating host cell innate immunity to regulate the immune response against many RNA viruses. We previously identified that a small molecule compound, KIN1148, led to the activation of IFN regulatory factor 3 (IRF3) and served to enhance protection against influenza A virus (IAV) A/California/04/2009 infection. We have now determined direct binding of KIN1148 to RIG-I to drive expression of IFN regulatory factor 3 and NF-κB target genes, including specific immunomodulatory cytokines and chemokines. Intriguingly, KIN1148 does not lead to ATPase activity or compete with ATP for binding but activates RIG-I to induce antiviral gene expression programs distinct from type I IFN treatment. When administered in combination with a vaccine against IAV, KIN1148 induces both neutralizing Ab and IAV-specific T cell responses compared with vaccination alone, which induces comparatively poor responses. This robust KIN1148-adjuvanted immune response protects mice from lethal A/California/04/2009 and H5N1 IAV challenge. Importantly, KIN1148 also augments human CD8+ T cell activation. Thus, we have identified a small molecule RIG-I agonist that serves as an effective adjuvant in inducing noncanonical RIG-I activation for induction of innate immune programs that enhance adaptive immune protection of antiviral vaccination.
(Copyright © 2023 by The American Association of Immunologists, Inc.)
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معلومات مُعتمدة: 75N92020D00005 United States HL NHLBI NIH HHS; U01 AI150747 United States AI NIAID NIH HHS; P51 OD010425 United States OD NIH HHS; HHSN272200900035C United States AI NIAID NIH HHS; 75N99020D00005 United States OF ORFDO NIH HHS; 17POST33660907 United States AHA American Heart Association-American Stroke Association; K22 AI146141 United States AI NIAID NIH HHS; P01 AI097092 United States AI NIAID NIH HHS; 75N93021C00014 United States AI NIAID NIH HHS; HHSN272201400055C United States AI NIAID NIH HHS; 75N93023D00005 United States AI NIAID NIH HHS; 75N93022D00005 United States AI NIAID NIH HHS; HHSN272201400006C United States AI NIAID NIH HHS; 75N95020D00005 United States DA NIDA NIH HHS; 75N93019C00046 United States AI NIAID NIH HHS; U01 AI151698 United States AI NIAID NIH HHS; 75N93019C00051 United States AI NIAID NIH HHS; R01 AI143265 United States AI NIAID NIH HHS; U19 AI100625 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Influenza Vaccines)
EC 3.6.4.13 (DEAD Box Protein 58)
0 (Interferon Regulatory Factor-3)
0 (Adjuvants, Immunologic)
0 (Antiviral Agents)
تواريخ الأحداث: Date Created: 20230320 Date Completed: 20230419 Latest Revision: 20240901
رمز التحديث: 20240901
مُعرف محوري في PubMed: PMC10149148
DOI: 10.4049/jimmunol.2300026
PMID: 36939421
قاعدة البيانات: MEDLINE
الوصف
تدمد:1550-6606
DOI:10.4049/jimmunol.2300026