دورية أكاديمية
أعرض في EDS

Development of a Molecular Adjuvant to Enhance Antigen-Specific CD8 + T Cell Responses.

التفاصيل البيبلوغرافية
العنوان: Development of a Molecular Adjuvant to Enhance Antigen-Specific CD8 + T Cell Responses.
المؤلفون: Halbroth BR; The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford, United Kingdom. benedict@halbroth.com., Sebastian S; The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford, United Kingdom., Poyntz HC; The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford, United Kingdom., Bregu M; The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford, United Kingdom., Cottingham MG; The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford, United Kingdom., Hill AVS; The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford, United Kingdom., Spencer AJ; The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford, United Kingdom. alex.spencer@ndm.ox.ac.uk.
المصدر: Scientific reports [Sci Rep] 2018 Oct 09; Vol. 8 (1), pp. 15020. Date of Electronic Publication: 2018 Oct 09.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Antigens, Protozoan/*immunology , CD8-Positive T-Lymphocytes/*immunology , Malaria Vaccines/*immunology , Malaria, Falciparum/*immunology, Adjuvants, Immunologic/administration & dosage ; Adjuvants, Pharmaceutic/administration & dosage ; Animals ; Antibodies, Protozoan/immunology ; Antigens, Differentiation, B-Lymphocyte/immunology ; Autoimmunity/drug effects ; CD8-Positive T-Lymphocytes/virology ; Epitopes/immunology ; Histocompatibility Antigens Class II/immunology ; Humans ; Malaria, Falciparum/parasitology ; Malaria, Falciparum/prevention & control ; Plasmodium falciparum/immunology ; Plasmodium falciparum/pathogenicity ; Protozoan Proteins/immunology ; Vaccinia virus/genetics
مستخلص: Despite promising progress in malaria vaccine development, an efficacious subunit vaccine against P. falciparum remains to be licensed and deployed. This study aimed to improve on the immunogenicity of the leading liver-stage vaccine candidate (ChAd63-MVA ME-TRAP), known to confer protection by eliciting high levels of antigen-specific CD8 + T cells. We previously showed fusion of ME-TRAP to the human MHC class II invariant chain (Ii) could enhance CD8 + T cell responses in non-human primates, but did not progress to clinical testing due to potential risk of auto-immunity by vaccination of humans with a self-antigen. Initial immunogenicity analyses of ME-TRAP fused to subdomains of the Ii showed that the Ii transmembrane domain alone can enhance CD8 + T cell responses. Subsequently, truncated Ii sequences with low homology to human Ii were developed and shown to enhance CD8 + T cell responses. By systematically mutating the TM domain sequence, multimerization of the Ii chain was shown to be important for immune enhancement. We subsequently identified several proteins from a variety of microbial pathogens with similar characteristics, that also enhance the CD8 + T cell response and could therefore be used in viral vector vaccines when potent cell mediated immunity is required.
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; 104750/Z/14/Z United Kingdom WT_ Wellcome Trust; 095540/Z/11/Z United Kingdom WT_ Wellcome Trust
المشرفين على المادة: 0 (Adjuvants, Immunologic)
0 (Adjuvants, Pharmaceutic)
0 (Antibodies, Protozoan)
0 (Antigens, Differentiation, B-Lymphocyte)
0 (Antigens, Protozoan)
0 (Epitopes)
0 (Histocompatibility Antigens Class II)
0 (Malaria Vaccines)
0 (Protozoan Proteins)
0 (invariant chain)
تواريخ الأحداث: Date Created: 20181011 Date Completed: 20191030 Latest Revision: 20240314
رمز التحديث: 20240314
مُعرف محوري في PubMed: PMC6177389
DOI: 10.1038/s41598-018-33375-1
PMID: 30301933
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-018-33375-1