دورية أكاديمية
أعرض في EDS

A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.

التفاصيل البيبلوغرافية
العنوان: A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.
المؤلفون: Edwards KR; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Global Health, University of Washington, Seattle, WA, USA., Malhi H; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Schmidt K; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Davis AR; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Homad LJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Warner NL; HDT Bio, Seattle, WA, USA., Chhan CB; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Global Health, University of Washington, Seattle, WA, USA., Scharffenberger SC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA., Gaffney K; HDT Bio, Seattle, WA, USA., Hinkley T; HDT Bio, Seattle, WA, USA., Potchen NB; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Global Health, University of Washington, Seattle, WA, USA., Wang JY; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Price J; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA., McElrath MJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Medicine, University of Washington, Seattle, WA, USA., Olson J; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA., King NP; Department of Biochemistry, University of Washington, Seattle, WA, USA.; Institute for Protein Design, University of Washington, Seattle, WA, USA., Lund JM; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Global Health, University of Washington, Seattle, WA, USA., Moodie Z; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Erasmus JH; HDT Bio, Seattle, WA, USA., McGuire AT; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. amcguire@fredhutch.org.; Department of Global Health, University of Washington, Seattle, WA, USA. amcguire@fredhutch.org.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. amcguire@fredhutch.org.
المصدر: NPJ vaccines [NPJ Vaccines] 2024 Jun 26; Vol. 9 (1), pp. 120. Date of Electronic Publication: 2024 Jun 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Nature in partnership with the Sealy Center for Vaccine Development Country of Publication: England NLM ID: 101699863 Publication Model: Electronic Cited Medium: Internet ISSN: 2059-0105 (Electronic) Linking ISSN: 20590105 NLM ISO Abbreviation: NPJ Vaccines Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [London] : Springer Nature in partnership with the Sealy Center for Vaccine Development, [2016]-
مستخلص: Epstein-Barr virus (EBV) is associated with several malignancies, neurodegenerative disorders and is the causative agent of infectious mononucleosis. A vaccine that prevents EBV-driven morbidity and mortality remains an unmet need. EBV is orally transmitted, infecting both B cells and epithelial cells. Several virally encoded proteins are involved in entry. The gH/gL glycoprotein complex is essential for infectivity irrespective of cell type, while gp42 is essential for infection of B cells. gp350 promotes viral attachment by binding to CD21 or CD35 and is the most abundant glycoprotein on the virion. gH/gL, gp42 and gp350, are known targets of neutralizing antibodies and therefore relevant immunogens for vaccine development. Here, we developed and optimized the delivery of several alphavirus-derived replicon RNA (repRNA) vaccine candidates encoding gH/gL, gH/gL/gp42 or gp350 delivered by a cationic nanocarrier termed LION™. The lead candidate, encoding full-length gH/gL, elicited high titers of neutralizing antibodies that persisted for at least 8 months and a vaccine-specific CD8 + T cell response. Transfer of vaccine-elicited IgG protected humanized mice from EBV-driven tumor formation and death following high-dose viral challenge. These data demonstrate that LION/repRNA-gH/gL is an ideal candidate vaccine for preventing EBV infection and/or related malignancies in humans.
(© 2024. The Author(s).)
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معلومات مُعتمدة: T32 AI007509 United States AI NIAID NIH HHS; P30 CA015704 United States CA NCI NIH HHS; 5T32AI007509 Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID); R01 CA285227 United States CA NCI NIH HHS; R01CA285227 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI); R01 AI147846 United States AI NIAID NIH HHS; R01AI147846 Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID); P30 AI027757 United States AI NIAID NIH HHS
تواريخ الأحداث: Date Created: 20240626 Latest Revision: 20240629
رمز التحديث: 20240629
مُعرف محوري في PubMed: PMC11208421
DOI: 10.1038/s41541-024-00907-y
PMID: 38926438
قاعدة البيانات: MEDLINE
الوصف
تدمد:2059-0105
DOI:10.1038/s41541-024-00907-y